Biosensors and Nanotheranostics

1. Introduction

Over the past few decades, nanoscience, materials engineering and biomedical research have converged in ways that are changing how disease is detected, treated and repaired (Elayan et al., 2016; Shi et al., 2010). The defining feature of this convergence is scale. Nanotechnology concerns structures whose functional dimensions usually lie between 1 and 100 nm, a range in which physical, chemical and biological behaviour departs markedly from that of the same material in bulk (Alexis et al., 2008; Elayan et al., 2016; Jin et al., 2017). The size range is not arbitrary from a biological point of view. Genomic nucleic acids, functional proteins, cell-membrane receptors and viral particles all operate at the nanometre scale, so engineered nanomaterials share a structural congruence with cellular and subcellular components that conventional drugs and devices lack (Jayaraman et al., 2021; Jin et al., 2017; Morris et al., 2014).

This spatial compatibility comes with several further advantages. Nanomaterials have very high surface-area-to-volume ratios and surfaces whose chemistry can be tuned almost at will; depending on composition, they may also display quantum confinement, plasmonic resonance or superparamagnetism (Azmi & Elgharbawy, 2021; Jayabal, 2025; Kazemi et al., 2024; Pardeshi & Souto, 2019). Taken together, these properties allow a single particle to carry a drug, a targeting ligand and an imaging label at once, which is why nanotechnology is increasingly described as a cornerstone of precision medicine (Pardeshi & Souto, 2019; Singh, 2025).

The need for such tools follows from the shortcomings of conventional interventions. Many small-molecule drugs have poor aqueous solubility, are cleared rapidly by the kidney or liver, distribute non-specifically through the body, show low oral bioavailability and cause considerable systemic toxicity (Gopi et al., 2021; Jayaraman et al., 2021; Morris et al., 2014). Diagnosis presents a parallel problem. The limited sensitivity and specificity of conventional analytical methods often allow malignant solid tumours, vascular occlusions and degenerative tissue disease to progress to advanced stages before clinical intervention begins (Gopi et al., 2021; Leucuta, 2010; Morris et al., 2014). Nanomedicine addresses both bottlenecks by providing nanoscale vehicles that can cross dense extracellular matrices, negotiate the blood–brain barrier and evade the body's clearance mechanisms long enough to reach their targets (Azmi & Elgharbawy, 2021; Morris et al., 2014; Singh, 2025).

The field has since diversified into four connected areas of application (Figure 1). Nanodiagnostics uses ultrasensitive biosensors, lab-on-a-chip microfluidics and molecular imaging probes to detect disease biomarkers far earlier than before (Ammar et al., 2025; Kumar et al., 2021). Targeted drug delivery employs liposomes, polymeric and lipid nanoparticles, dendrimers, nanogels and metal–organic frameworks to improve pharmacokinetics and limit off-target harm (Kazemi et al., 2024; Venkatraman & Boey, 2012). In oncology, theranostic platforms combine imaging and therapy in a single construct and add photothermal, photodynamic and catalytic modalities to the therapeutic repertoire (Deswal et al., 2021; Rana & Bhatnagar, 2021; Yuan et al., 2026). Regenerative medicine, finally, uses nanostructured scaffolds that imitate the native extracellular matrix to guide tissue repair (Chakraborty et al., 2025; Jayabal, 2025).

Preclinical success has not translated smoothly into clinical use. Long-term tissue accumulation, systemic organ toxicity, off-target immunogenicity and unpredictable clearance kinetics remain serious concerns (Chakraborty et al., 2025; Jayabal, 2025; Jayaraman et al., 2021). Reproducible, large-scale synthesis of complex multifunctional nanoparticles with stable surface charge is technically demanding (Jayabal, 2025; Rana & Bhatnagar, 2021), and standardised toxicological screening and clear regulatory frameworks are still lacking (Ammar et al., 2025; Jayabal, 2025). Much of the existing literature also treats diagnostics, delivery, oncology and regeneration separately, which obscures the shared design principles and shared obstacles that cut across them.

This review therefore brings the four domains together within a single analytical frame. Its specific objectives are to (i) examine how particle size, geometry, surface charge and composition govern interactions at the nano–bio interface and transport across biological barriers (Alexis et al., 2008; Jayabal, 2025; Kazemi et al., 2024; Singh, 2025); (ii) evaluate the engineering principles and reported performance of nanoscale biosensors, surface-enhanced Raman scattering (SERS) platforms, point-of-care microfluidics and contrast agents for magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET) and optical imaging (Ammar et al., 2025; Kumar et al., 2021; Leucuta, 2010; Morris et al., 2014); (iii) compare passive accumulation through the enhanced permeability and retention (EPR) effect with active ligand–receptor targeting and stimuli-responsive release across organic, inorganic and hybrid carriers (Bamrungsap et al., 2012; Jain et al., 2005; Leucuta, 2010; Singh, 2025); (iv) review multifunctional theranostic, nanozyme-based and phototherapeutic strategies for modulating the tumour microenvironment (Ammar et al., 2025; Deshwal et al., 2024; Pardeshi & Souto, 2019; Rana & Bhatnagar, 2021; Yuan et al., 2026); (v) outline the role of nanofibrous scaffolds, nanomineral-enhanced hydrogels and 3D/4D bio-inks in regenerative medicine (Ammar et al., 2025; Chakraborty et al., 2025; Jayabal, 2025; Shi et al., 2010); and (vi) identify the toxicological, manufacturing and regulatory gaps that still separate nanomedicine from routine clinical adoption (Ammar et al., 2025; Chakraborty et al., 2025; Jayabal, 2025; Rana & Bhatnagar, 2021).

2. Nanomedicine in Diagnostics, Targeted Delivery, Cancer Theranostics, and Regenerative Medicine

2.1 Conceptual Foundations of Nanomedicine

2.1.1 From Conventional Pharmacology to Nanoscale Design

The application of nanotechnology to biology and clinical science, usually called nanomedicine, has produced a structural shift in how disease is diagnosed, treated and repaired (Elayan et al., 2016; Shi et al., 2010). Its starting point is a set of physiological and pharmacological constraints that conventional interventions struggle to overcome: poor aqueous solubility of many organic drug molecules, rapid hepatic or renal clearance, systemic off-target toxicity, low bioavailability and an inability to cross biological boundaries such as the blood–brain barrier (Gopi et al., 2021; Kazemi et al., 2024; Singh, 2025). Nanotechnology tackles these barriers by building functional architectures at the sub-micron scale, typically between 1 and 100 nm (Alexis et al., 2008; Jin et al., 2017). At this scale, engineered structures match the dimensions of fundamental biological machinery, including nucleic acid sequences, cellular enzymes, transmembrane receptors and extracellular matrix proteins (Jin et al., 2017; Morris et al., 2014; Shi et al., 2010).

2.1.2 Physicochemical Advantages at the Nanoscale

Materials at the nanoscale display physicochemical, quantum and mechanical behaviour that differs sharply from their macroscale counterparts (Azmi & Elgharbawy, 2021; Singh, 2025). Their very high surface-area-to-volume ratio allows dense surface functionalisation with drugs, protective hydrophilic coatings, imaging agents and site-specific targeting ligands (Bamrungsap et al., 2012; Pardeshi & Souto, 2019). Engineered nanomaterials also show favourable transport behaviour in the body, including prolonged circulation and passive accumulation in diseased tissue through leaky microvasculature, the phenomenon known as the EPR effect (Alexis et al., 2008; Leucuta, 2010; Venkatraman & Boey, 2012). These properties, summarised in Figure 1, underpin every application discussed below. The reported size windows of the main platform classes, and their relation to the fenestration cut-off of tumour vessels, are compared in Figure 2.

2.2 Nanodiagnostics and High-Sensitivity Biosensing

2.2.1 Rationale for Nanoscale Diagnostics

Early and accurate detection is essential if mortality is to fall and treatment is to be tailored to the individual (Kumar et al., 2021; Singh, 2025). Nanotechnology has changed molecular diagnostics through highly sensitive biosensors, lab-on-a-chip microfluidic architectures and advanced molecular imaging probes (Ammar et al., 2025; Morris et al., 2014; Singh, 2025). Functionalised gold nanoparticles, carbon nanotubes, quantum dots and SERS nanoprobes allow biomarkers such as microRNAs, circulating tumour DNA (ctDNA), protein antigens and circulating tumour cells (CTCs) to be identified at picogram-per-millilitre concentrations (Ammar et al., 2025; Kumar et al., 2021; Leucuta, 2010). The principal diagnostic platforms, their sensing mechanisms and reported performance are summarised in Table 2 and Figure 3.

2.2.2 Quantum Dots for Multiplexed Optical Imaging

Semiconductor quantum dots (QDs), nanocrystals usually composed of cadmium selenide, zinc sulphide or indium phosphide, have become important fluorophores for non-invasive molecular imaging (Jayaraman et al., 2021; Kumar et al., 2021; Pardeshi & Souto, 2019). Conventional organic dyes suffer from narrow excitation bands, broad emission spectra and rapid photobleaching. QDs, by contrast, combine broad absorption with narrow, symmetrical and size-tunable emission peaks, high quantum yields and strong resistance to photobleaching (Azmi & Elgharbawy, 2021; Singh, 2025). When conjugated to antibodies, aptamers or peptides, QDs support multiplexed biomarker profiling, allowing simultaneous quantitative tracking of tumour markers such as human epidermal growth factor receptor 2 (HER2), mucin-16 and prostate-specific membrane antigen (PSMA) in serum or living tissue (Ammar et al., 2025; Jayaraman et al., 2021; Kumar et al., 2021).

2.2.3 Surface-Enhanced Raman Scattering Nanoprobes

SERS nanoprobes built from noble-metal nanoparticles, chiefly gold and silver, strongly amplify local electromagnetic fields under laser excitation (Kumar et al., 2021; Pardeshi & Souto, 2019). This amplification arises from localised surface plasmon resonance at metallic

Figure 1. Conceptual overview of nanotechnology across the four clinical domains reviewed. Engineered materials of 1–100 nm (centre) share six physicochemical properties, shown in the surrounding boxes, that underpin the four application pillars at the corners: diagnostics and biosensing, drug delivery and targeting, oncology and theranostics, and regenerative therapy. Representative technologies are listed under each pillar. The bottom bar lists the translational filters (toxicity and clearance, reproducible scale-up, EPR heterogeneity and regulation) common to all four domains. Compiled from the sources cited in Sections 2.1–2.6.

Figure 2. Reported size ranges of diagnostic and therapeutic nanoplatforms relative to the nanoscale domain and the tumour fenestration window. Bars show the size range of each platform class reported in Tables 1 and 2, on a logarithmic scale. The blue band marks the nanoscale domain (1–100 nm); the red band marks the tumour vascular pore cut-off (100–700 nm) that permits passive extravasation through the EPR effect (Alexis et al., 2008; Venkatraman & Boey, 2012). Most carriers lie wholly or partly within the passable range, whereas quantum dots fall well below it. Colour separates diagnostic probes from therapeutic carriers.

nanogaps and allows trace biomarkers to be identified, including circulating microRNAs, mutated ctDNA and volatile organic compounds (VOCs) in exhaled breath associated with early-stage lung cancer, at picogram-per-millilitre sensitivities (Kumar et al., 2021; Morris et al., 2014).

2.2.4 Multimodal Contrast Agents and Liquid Biopsy Platforms

Nanotechnology also improves the clinical imaging modalities of MRI, CT and PET (Deswal et al., 2021; Jin et al., 2017; Morris et al., 2014). Superparamagnetic iron oxide nanoparticles (SPIONs) serve as negative T₂ contrast agents in MRI, offering high spatial resolution without the systemic toxicity or nephrogenic risk associated with gadolinium-based chelates (Jayaraman et al., 2021; Singh, 2025). Functionalised with targeting moieties such as amino-terminal fragments of urokinase plasminogen activator (uPA) or cyclic RGD peptides, SPIONs accumulate selectively in malignant tissue, allowing tumour boundaries to be defined precisely and micrometastases to be detected non-invasively (Deswal et al., 2021; Jayaraman et al., 2021). Integrated microfluidic platforms extend these gains to liquid biopsy. NanoVelcro substrates, in which silicon nanowires are coated with aptamers or antibodies, isolate rare CTCs and tumour-derived exosomes directly from patient blood, supporting early cancer staging and the monitoring of treatment response (Jayaraman et al., 2021; Kumar et al., 2021; Morris et al., 2014).

2.3 Targeted Drug Delivery and Stimuli-Responsive Nanocarriers

2.3.1 Pharmacokinetic Rationale for Nanocarriers

The clinical value of many potent drugs is limited by unfavourable pharmacokinetics, systemic side effects and inadequate accumulation in target tissue (Bamrungsap et al., 2012; Gopi et al., 2021). Engineered nanocarriers ease these limitations by encapsulating labile or hydrophobic active ingredients, protecting them from pre-systemic enzymatic degradation and controlling their release at the intended site (Alexis et al., 2008; Bamrungsap et al., 2012; Jin et al., 2017). Targeted delivery has consequently become one of the most firmly established applications of nanomedicine (Azmi & Elgharbawy, 2021; Elayan et al., 2016; Venkatraman & Boey, 2012). The three main localisation strategies are illustrated in Figure 4, and the principal carrier classes are compared in Table 1.

2.3.2 Passive Accumulation Through the EPR Effect

Passive targeting exploits the pathophysiology of solid tumours and inflamed tissue (Alexis et al., 2008; Azmi & Elgharbawy, 2021). Rapid tumour angiogenesis produces fenestrated microvasculature with pore cut-offs of 100–700 nm, accompanied by dysfunctional lymphatic drainage (Alexis et al., 2008; Leucuta, 2010; Venkatraman & Boey, 2012). Long-circulating nanocarriers therefore extravasate and accumulate in the tumour interstitium (Ammar et al., 2025; Bamrungsap et al., 2012; Leucuta, 2010). To delay recognition and clearance by the reticuloendothelial system (RES), carriers are commonly coated with hydrophilic polymers such as polyethylene glycol (PEGylation), which forms a steric hydration barrier and extends circulation half-life (Bamrungsap et al., 2012; Ding et al., 2022; Leucuta, 2010).

2.3.3 Active Ligand–Receptor Targeting

Because EPR-mediated accumulation is heterogeneous, active targeting adds affinity ligands to the carrier surface. These include monoclonal antibody fragments, nucleic acid aptamers, small-molecule vitamins such as folic acid and cell-penetrating peptides (Bamrungsap et al., 2012; Deswal et al., 2021; Jain et al., 2005; Leucuta, 2010; Venkatraman & Boey, 2012). The ligands bind receptors that are overexpressed on target cells, such as the epidermal growth factor receptor (EGFR), HER2, the folate receptor or integrin αvβ3. Binding triggers receptor-mediated endocytosis and favours intracellular drug delivery while sparing healthy cells (Azmi & Elgharbawy, 2021; Bamrungsap et al., 2012; Deswal et al., 2021; Singh, 2025).

2.3.4 Architectures of Organic, Inorganic and Hybrid Nanocarriers

A wide range of organic, inorganic and hybrid carriers has been developed to meet different pharmacological demands (Table 1). Liposomes and lipid nanoparticles consist of phospholipid bilayers enclosing an aqueous core, so they can carry hydrophilic drugs inside and lipophilic agents within the membrane; approved formulations such as Doxil® markedly reduce cardiotoxicity compared with free doxorubicin (Bamrungsap et al., 2012; Jayaraman et al., 2021). Polymeric nanoparticles and nanogels built from poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA)

Table 1. Comparative classification of the major nanocarrier platforms used in drug delivery and therapeutics. The table compares six classes of nanocarrier according to their physicochemical structure and reported size range, the mechanism by which they load and localise their cargo, and their main pharmacokinetic advantages. It also lists the biological limitations and toxicity concerns reported for each class, together with representative drugs or cargoes, including approved formulations. All carriers can exploit passive accumulation through the enhanced permeability and retention (EPR) effect, while most can be surface-modified for active, ligand-directed targeting. Abbreviations: mAb, monoclonal antibody; PEG, polyethylene glycol; RES, reticuloendothelial system; MOF, metal–organic framework; PLGA, poly(lactic-co-glycolic acid); PLA, polylactic acid; PCL, polycaprolactone.

Table 2. Nanotechnology-based platforms for high-sensitivity biomarker sensing and diagnostic imaging. Six diagnostic modalities are compared in terms of the nanomaterial used, the biomarker or pathology detected, the physical principle by which the signal is generated or amplified, and the key performance metrics reported in the included sources. The platforms draw on quantum confinement, localised surface plasmon resonance (LSPR), superparamagnetism, electrocatalysis and microfluidic capture. Performance values are transcribed as reported and were mostly obtained in analytical or preclinical settings; only the liquid-biopsy sensitivities derive from clinical samples. Abbreviations: QD, quantum dot; SPION, superparamagnetic iron oxide nanoparticle; CTC, circulating tumour cell; ctDNA, circulating tumour DNA; VOC, volatile organic compound; LOD, limit of detection.

or crosslinked hydrogel networks are biocompatible and biodegradable, and they protect unstable macromolecules such as siRNA and proteins (Deswal et al., 2021; Gupta & Sharma, 2024; Jin et al., 2017; Kazemi et al., 2024). Nanoscale metal–organic frameworks (nanoMOFs), assembled from metal nodes and organic linkers, provide large internal surface areas and very high drug payloads (Deshwal et al., 2024; Ding et al., 2022). At the most experimental end, self-propelled nanobots capable of autonomous movement through biological fluids are being explored for deep penetration into solid tumours (Jayaraman et al., 2021; Kazemi et al., 2024).

2.3.5 Stimuli-Responsive Release

"Smart" nanocarriers release their cargo in response to physiological or external triggers, which allows release to be controlled in space and time (Azmi & Elgharbawy, 2021; Jayabal, 2025; Singh, 2025). Endogenous triggers exploit features of the diseased microenvironment: the acidic extracellular pH of tumours (approximately 6.2–6.8), elevated intracellular reducing agents such as glutathione (GSH) and overexpressed enzymes such as matrix metalloproteinases (MMPs) (Azmi & Elgharbawy, 2021; Ding et al., 2022; Singh, 2025). External triggers use non-invasive physical inputs, including focused near-infrared (NIR) light, magnetic fields, low-intensity ultrasound and hyperthermia, to release the payload on demand (Azmi & Elgharbawy, 2021; Gharpure et al., 2015; Jayaraman et al., 2021).

2.4 Oncology, Theranostics and Tumour Microenvironment Modulation

2.4.1 Multifunctional Cancer Theranostics

In oncology, nanomedicine offers integrated solutions that combine treatment with monitoring (Ammar et al., 2025; Deswal et al., 2021; Gharpure et al., 2015). The theranostic concept places imaging agents and therapeutic payloads in a single multifunctional platform, so that tumours can be visualised, drug accumulation tracked in real time and therapeutic efficacy assessed non-invasively (Pardeshi & Souto, 2019; Rana & Bhatnagar, 2021). Gold-coated iron oxide nanostars, porphyrinic nanoMOFs and quantum dot–aptamer conjugates are representative examples, allowing tumour margins to be outlined by optical or magnetic imaging while treatment proceeds (Ammar et al., 2025; Deswal et al., 2021; Ding et al., 2022; Pardeshi & Souto, 2019). The main theranostic and microenvironment-directed strategies are collated in Table 3 and illustrated in Figure 5.

2.4.2 Photothermal and Photodynamic Therapy

Beyond conventional chemotherapy, nanotechnology supports minimally invasive treatment modalities. Photothermal therapy (PTT) uses NIR-absorbing nanoparticles such as gold nanorods, graphene oxide and copper sulphide to convert light into localised hyperthermia above 42 °C, lysing tumour cells while largely sparing surrounding healthy tissue (Ammar et al., 2025; Gharpure et al., 2015; Pardeshi & Souto, 2019). Photodynamic therapy (PDT) relies on photosensitiser-loaded nanoparticles that, under irradiation at specific wavelengths, transfer energy to molecular oxygen and generate cytotoxic reactive oxygen species (ROS), principally singlet oxygen (¹O₂) (Ammar et al., 2025; Gopi et al., 2021; Singh, 2025).

2.4.3 Catalytic Nanozymes and Chemodynamic Therapy

Catalytic nanomaterials, or nanozymes, including iron oxide and cerium oxide nanoparticles, copper-based MOFs and single-atom catalysts, mimic natural enzymes such as peroxidase, catalase, oxidase and superoxide dismutase (Deshwal et al., 2024; Yuan et al., 2026). In chemodynamic therapy (CDT), nanozymes drive Fenton-like reactions in the tumour microenvironment (TME), converting the hydrogen peroxide (H₂O₂) that tumours overproduce into hydroxyl radicals (•OH) and depleting intratumoural GSH (Deshwal et al., 2024; Deswal et al., 2021). Catalase-like nanozymes can also decompose H₂O₂ into molecular oxygen, relieving the hypoxia that blunts PDT, radiotherapy and chemotherapy (Deshwal et al., 2024; Ding et al., 2022). Sonodynamic therapy (SDT) extends the same logic to ultrasound, which penetrates more than 10 cm of tissue and can activate sonosensitisers deep within the body (Deshwal et al., 2024).

2.4.4 Immunomodulation of the Tumour Microenvironment

Nanoparticles can also reshape the immunosuppressive components of the TME. Iron oxide nanoparticles such as ferumoxytol promote pro-inflammatory macrophage polarisation, shifting tumour-associated macrophages (TAMs) from an immunosuppressive M2 phenotype towards an anti-tumoural M1 state (Chakraborty et al., 2025; Deswal et al., 2021). Nano-enabled phototherapies, moreover, induce immunogenic cell death, releasing

tumour neoantigens and damage-associated molecular patterns (DAMPs) that stimulate systemic anti-tumour immunity (Deshwal et al., 2024). Green-synthesised and bioinspired nanocomposites are being developed with the same aim of disrupting the TME while limiting systemic side effects (Ammar et al., 2025; Gopi et al., 2021; Rana & Bhatnagar, 2021).

2.5 Regenerative Medicine and Biomimetic Tissue Engineering

2.5.1 The Extracellular Matrix as a Design Template

Regenerative medicine seeks to repair or replace damaged tissues and organs by combining cells, biomimetic scaffolds and microenvironmental cues (Azmi & Elgharbawy, 2021; Jayabal, 2025; Shi et al., 2010). The native extracellular matrix (ECM) is a complex network of nanoscale protein fibres that directs cell adhesion, migration, proliferation and stem cell lineage commitment (Jayabal, 2025; Leucuta, 2010; Shi et al., 2010). Reproducing this architecture has therefore become a central design goal. Table 4 and Figure 6 summarise how different nanomaterial strategies have been matched to particular tissues.

2.5.2 Nanofibrous Scaffolds and ECM Mimicry

Synthetic scaffolds produced by electrospinning, self-assembly or phase separation emulate the architecture of native collagen fibrils (Jayabal, 2025; Shi et al., 2010). Nanofibrous membranes made from polycaprolactone (PCL), PLGA, chitosan or silk fibroin offer high surface-area-to-volume ratios and interconnected porosity (Jayabal, 2025; Leucuta, 2010). These structural features support cell attachment, nutrient transport and cell alignment in applications ranging from skin wound healing to peripheral nerve regeneration and vascular graft construction (Jayabal, 2025).

2.5.3 Nanominerals, Conductive Nanocomposites and Bioactive Hydrogels

Inorganic nanominerals, including nanohydroxyapatite (nHA), bioactive glass nanoparticles, two-dimensional synthetic nanosilicates (Laponite®) and cerium oxide nanoparticles, improve the mechanical properties and bioactivity of polymeric hydrogels (Chakraborty et al., 2025; Jayabal, 2025). Nanosilicates and nHA reinforce the structure while releasing osteoinductive ions (Ca²⁺, PO₄³⁻ and Si⁴⁺) that trigger osteogenic differentiation of stem cells without added growth factors (Chakraborty et al., 2025; Jayabal, 2025). Carbon-based nanomaterials such as carbon nanotubes (CNTs) and graphene oxide (GO) introduce electrical conductivity into scaffolds, promoting neural axon outgrowth and synchronised contraction of cardiac tissue (Jayabal, 2025). Catalytic nanozymes are also being investigated for bone regeneration, where their redox activity may help to control local oxidative stress (Yuan et al., 2026).

2.5.4 Nanoengineered Bio-Inks for 3D and 4D Bioprinting

Adding nanomaterials to bio-inks for 3D bioprinting improves printability, shear-thinning behaviour, structural fidelity and post-printing cell viability (Chakraborty et al., 2025; Jayabal, 2025). Four-dimensional bioprinting goes a step further by incorporating stimuli-responsive nanocomposites, producing constructs that change shape or function over time in response to physiological signals (Jayabal, 2025). Combined with 3D/4D printing, these biomimetic constructs are advancing functional regeneration of bone, cartilage, skin, neural and vascular tissue (Ammar et al., 2025; Jayabal, 2025).

2.6 Translational Bottlenecks Identified in the Literature

2.6.1 Safety, Manufacturing and Biological Variability

Despite extensive preclinical validation, the clinical translation of nanomedicine faces technical, toxicological and regulatory obstacles (Chakraborty et al., 2025; Jayabal, 2025). Non-biodegradable nanomaterials may accumulate in tissue over the long term and cause oxidative stress, immune activation or organ toxicity (Ammar et al., 2025; Chakraborty et al., 2025; Jayabal, 2025). Scalable, batch-to-batch synthesis of complex multifunctional nanoparticles with consistent size distributions, drug loading and ligand densities remains difficult (Chakraborty et al., 2025; Jayabal, 2025; Morris et al., 2014). Microvascular permeability also varies between patients and tumour histologies, which limits the predictability of passive targeting (Deswal et al., 2021; Gopi et al., 2021; Morris et al., 2014).

2.6.2 Regulatory Needs and Emerging Solutions

Standardised safety evaluation, agreed characterisation protocols and clear regulatory guidance are needed before nanomedicines can be adopted routinely (Ammar et al., 2025; Chakraborty et al., 2025; Jayabal, 2025). Several lines of work may help: green synthesis, biomimetic cell-membrane camouflage, artificial intelligence-guided particle design and personalised diagnostic profiling are all expected to ease these hurdles and move nanomedicine towards patient-tailored care (Ammar et al., 2025; Azmi & Elgharbawy, 2021; Ding et al., 2022; Jayabal, 2025).

3. Methods

3.1 Review Design and Reporting Framework

This study was designed as a structured narrative review covering four application domains of medical nanotechnology: diagnostics, drug delivery, oncology and regenerative therapy. A narrative rather than a meta-analytic design was chosen because the included evidence is heterogeneous. It spans conceptual reviews, edited book chapters and mechanistic preclinical studies, and outcome measures range from detection limits and loading capacities to cell viability and tumour regression, which cannot be pooled statistically (Jayaraman et al., 2021; Morris et al., 2014). To keep the process transparent and reproducible, the search, selection and data-charting steps were planned in advance and reported following the relevant items of the PRISMA 2020 statement adapted for narrative reviews, and the manuscript was checked against the Scale for the Assessment of Narrative Review Articles (SANRA). No protocol was registered, because narrative reviews are not eligible for registration in PROSPERO.

3.2 Information Sources

Literature was identified from three bibliographic databases, PubMed/MEDLINE, Scopus and Web of Science Core Collection, supplemented by Google Scholar and the publisher platforms SpringerLink, ScienceDirect and IEEE Xplore. Publisher platforms were included deliberately because a substantial share of the specialised nanomedicine literature appears in edited volumes and conference proceedings that are inconsistently indexed in PubMed, for example the chapters of the edited volume on nanomedicine for cancer diagnosis and therapy (Deswal et al., 2021; Gopi et al., 2021; Jayaraman et al., 2021; Kumar et al., 2021; Rana & Bhatnagar, 2021) and conference work on future healthcare applications (Elayan et al., 2016). Reference lists of all included sources were screened by hand (backward citation searching) to find further eligible records. The final search was run on March 2026.

3.3 Search Strategy

Search strings combined controlled vocabulary with free-text terms grouped into a core concept block and four domain blocks. In PubMed, the core block was ("Nanomedicine"[MeSH] OR "Nanoparticles"[MeSH] OR "Nanostructures"[MeSH] OR nanotechnolog*[tiab] OR nanomaterial*[tiab] OR nanoparticle*[tiab] OR nanocarrier*[tiab]). It was combined with AND with each of the following domain blocks: (a) diagnostics, (biosensor* OR "quantum dot*" OR "surface-enhanced Raman" OR SERS OR "contrast agent*" OR "liquid biopsy" OR "circulating tumor cell*"); (b) drug delivery, ("Drug Delivery Systems"[MeSH] OR liposom* OR "lipid nanoparticle*" OR dendrimer* OR nanogel* OR "metal-organic framework*" OR "enhanced permeability and retention" OR "stimuli-responsive"); (c) oncology, ("Neoplasms"[MeSH] OR theranostic* OR photothermal OR photodynamic OR chemodynamic OR sonodynamic OR nanozyme* OR "tumor microenvironment"); and (d) regenerative therapy, ("Tissue Engineering"[MeSH] OR "Regenerative Medicine"[MeSH] OR scaffold* OR electrospun OR nanomineral* OR bioprinting OR "extracellular matrix"). Equivalent strings were adapted to the syntax of Scopus (TITLE-ABS-KEY) and Web of Science (TS=). Searches were limited to English-language records published between January 2005 and March 2026, a window chosen to include the foundational work on aptamer-conjugated nanocarriers (Jain et al., 2005) together with the most recent nanozyme and regenerative studies (Jayabal, 2025; Yuan et al., 2026).

3.4 Eligibility Criteria

Records were eligible if they (i) were peer-reviewed journal articles, edited book chapters or peer-reviewed conference papers; (ii) dealt mainly with engineered materials whose functional dimensions lay in the nanoscale range, nominally 1–100 nm, with larger carriers accepted when they were explicitly described as nanocarriers (Alexis et al., 2008; Jin et al., 2017); (iii) reported a diagnostic, drug delivery, oncological, theranostic or regenerative application in human or animal biology, or the translational and safety issues of such applications; and (iv) provided enough mechanistic or performance detail to be charted. Records were excluded if they concerned only non-medical uses of nanomaterials (for example, electronics, catalysis for industrial chemistry or environmental remediation), were editorials, news items or abstracts without full text, or duplicated data already captured from a more complete source.

3.5 Study Selection

After the database exports had been merged, duplicates were removed in a reference manager Zotero 6. Titles and abstracts were screened against the eligibility criteria, and potentially relevant records were then assessed in full text. The final corpus comprised 28 sources: 20 journal articles, 7 book chapters and 1 conference paper.

3.6 Data Extraction and Charting

A standardised extraction form was used to chart each included record. The fields were: bibliographic details; application domain; nanomaterial class and composition; reported size range; fabrication or synthesis route; surface modification and targeting ligand; mechanism of action, signal transduction or release; biological target or biomarker; quantitative performance metrics (for example, limit of detection, clinical sensitivity, drug loading in wt%, cell viability); level of evidence (in vitro, in vivo animal, clinical or approved product); and reported limitations or toxicity concerns. Where a metric was reported in more than one source, the value was taken from the source that gave the most methodological detail, and the agreeing sources were cited alongside it. Quantitative values were transcribed exactly as reported, without conversion or re-analysis.

3.7 Synthesis Approach

Charted data were synthesised thematically. Records were first grouped into the four pre-specified domains, and within each domain into sub-themes that emerged from the data, such as passive versus active targeting, catalytic versus phototherapeutic modalities and mineral versus conductive scaffold additives. Four comparative tables were built from the extraction form: nanocarrier platforms (Table 1), diagnostic modalities (Table 2), theranostic and TME-remodelling strategies (Table 3) and regenerative nanomaterials (Table 4). Six figures were then drawn directly from the charted content. Figure 2 plots the size ranges reported in Table 1 and Table 2 on a logarithmic scale against the reported tumour fenestration window of 100–700 nm (Alexis et al., 2008; Venkatraman & Boey, 2012). Figure 6 is a presence–absence matrix of nanomaterial strategy against target tissue derived from Table 4. Figures were produced in Python 3 with the Matplotlib library (version 3.11), and no data points were added beyond those reported in the included sources. Cross-domain findings, including recurring translational barriers, were then compared narratively.

3.8 Appraisal of Sources and Handling of Uncertainty

Because the corpus is dominated by reviews and preclinical work, formal risk-of-bias tools designed for clinical trials were not applicable. Each source was instead appraised for relevance, recency, transparency of reported methods and whether its claims rested on primary data or on secondary citation. Statements resting on a single source, or on preclinical models only, are flagged as such in the synthesis and discussion. Level-of-evidence information from the extraction form (for example, "extensive preclinical validation" versus "FDA-approved") is reported in Table 3 so that readers can judge clinical maturity directly. Citations follow the American Psychological Association (APA) 7th edition, and all in-text citations correspond to entries in the reference list.

4. Synthesis of Findings: Cross-Domain Evidence on the Mechanisms and Performance of Medical Nanoplatforms

4.1 Overview of the Evidence Base

Read together, the 28 sources suggest that nanotechnology has widened what clinical medicine can do, though perhaps less evenly than the more enthusiastic accounts imply. The recurring theme is dimensional. Because engineered nanomaterials operate at 1–100 nm, the same scale as biomolecules, they appear able to overcome biological barriers, improve pharmacokinetics, increase diagnostic sensitivity and provide biomimetic cues for regeneration (Alexis et al., 2008; Jin et al., 2017; Shi et al., 2010) (Figure 1). How far each of these gains has been demonstrated, however, varies considerably between domains. The synthesis below follows the four domains in turn, beginning with drug delivery, where clinical evidence is strongest, and ending with regenerative biomaterials, where it is thinnest.

4.2 Pharmacokinetic Optimisation by Nanocarrier Systems

4.2.1 Encapsulation and Circulation

Across therapeutic platforms, nanoscale encapsulation consistently changes drug biodistribution and systemic toxicity (Table 1). Conventional small-molecule chemotherapeutics are cleared rapidly, dissolve poorly in water and cause considerable off-target harm (Gopi et al., 2021; Jayaraman et al., 2021). Encapsulating them in lipid, polymeric or inorganic carriers shields them from pre-systemic enzymatic degradation and extends circulation half-life (Bamrungsap et al., 2012; Kazemi et al., 2024; Wacker, 2019). The point is hardly contested in the corpus. What is less settled is how much of the benefit depends on where the carrier ultimately accumulates, which depends in turn on the targeting mechanism.

4.2.2 Passive Accumulation and the Role of Particle Geometry

Two broad mechanisms govern localisation (Figure 4). The first, passive accumulation through the EPR effect, rests on the fenestrated tumour microvasculature with pore cut-offs of 100–700 nm and on poor lymphatic drainage, which together allow long-circulating particles to extravasate and stay in the interstitium (Alexis et al., 2008; Leucuta, 2010; Venkatraman & Boey, 2012). Most carrier classes fall at least partly within this window (Figure 2), which is reassuring, although the overlap is not complete for the larger liposomal and polymeric formulations. Particle shape seems to matter as well. Non-spherical nanorods of 12–60 nm hydrodynamic diameter show more tumbling and rolling along vessel walls than spheres of the same volume, which favours extravasation (Alexis et al., 2008). PEGylation, by forming a steric hydration shell, slows uptake by the mononuclear phagocyte system in the liver and spleen and prolongs circulation considerably (Bamrungsap et al., 2012; Leucuta, 2010).

4.2.3 Active Targeting and Triggered Release

The second mechanism is an attempt to compensate for the variability of the first. Coating carriers with anti-HER2 antibodies, anti-CD133, cyclic RGD peptides or nucleic acid aptamers allows selective binding to overexpressed receptors and triggers receptor-mediated endocytosis (Alexis et al., 2008; Bamrungsap et al., 2012; Jain et al., 2005). Stimuli-responsive carriers add a further layer of control, releasing their payload in response to acidic intratumoural pH, elevated GSH or MMP activity, or to externally applied NIR light, ultrasound and alternating magnetic fields (Azmi & Elgharbawy, 2021; Ding et al., 2022; Singh, 2025). Whether the two approaches add together in patients, rather than only in mouse models, is something the corpus does not really resolve.

4.2.4 Comparative Performance of Carrier Classes

Among organic carriers, liposomes such as Doxil®/Caelyx® remain the most clinically validated class; they reduce the cardiotoxicity of doxorubicin substantially compared with the free drug (Bamrungsap et al., 2012; Jayaraman et al., 2021) (Table 1). Solid lipid and lipid nanoparticles appear well suited to hydrophobic drugs and labile RNA, as the approved siRNA formulation Onpattro™ shows (Jayaraman et al., 2021; Kazemi et al., 2024; Wacker, 2019). Polymeric nanoparticles and crosslinked nanogels load hydrophobic drugs and delicate nucleic acids efficiently and release them slowly, although burst release and acidic degradation products remain a concern (Gupta & Sharma, 2024; Jin et al., 2017; Kazemi et al., 2024). Dendrimers offer precise, monodisperse architectures, but unmodified cationic forms damage cell membranes (Gharpure et al., 2015; Kazemi et al., 2024). Among inorganic systems, nanoMOFs such as MIL-100, ZIF-8 and UiO-66 stand out for payloads of up to 50 wt% and for frameworks that respond to physiological pH. That capacity comes with a cost, however: the frameworks tend to amorphise under stress and are hard to reproduce from batch to batch (Ding et al., 2022).

4.3 Diagnostic Performance of Nanoscale Sensing Platforms

4.3.1 Optical Platforms: Quantum Dots and SERS

In diagnostics, nanomaterials exploit surface plasmon resonance, quantum confinement and magnetic susceptibility to detect trace biomarkers, in principle well before symptoms appear (Kumar et al., 2021; Singh, 2025) (Table 2; Figure 3). QD bioconjugates are reported to be roughly 30 times brighter than conventional organic dyes, enabling multiplexed profiling of low-abundance markers such as HER2, PSMA and CA125 in serum and tissue (Ammar et al., 2025; Jayaraman et al., 2021; Kumar et al., 2021). SERS probes made from gold or silver nanoparticles, sometimes combined with MOF or graphene supports, quantify breath VOCs and circulating microRNAs such as miRNA-155 at picogram-per-millilitre levels (Kumar et al., 2021; Morris et al., 2014). These are striking figures. Most were obtained in controlled analytical settings, however, and not in unselected patient cohorts.

4.3.2 Magnetic and Electrochemical Platforms

SPIONs (Fe₃O₄) and ferumoxytol act as T₂ contrast agents that avoid the nephrotoxicity of gadolinium chelates; when targeted with uPA fragments, they delineate tumour vascular boundaries and reveal micrometastases (Azmi & Elgharbawy, 2021; Deswal et al., 2021; Jayaraman et al., 2021) (Table 2). Photoelectrochemical sensors built from nanozyme-anchored SnO₂/CdS QDs or MoO₃@RGO nanohybrids report a limit of detection of 0.2 pg/mL for CYFRA 21-1 across a linear range of 0.001–200 ng/mL in

Figure 3. Workflow of five nanodiagnostic platforms, from nanomaterial to reported clinical read-out. Each row traces one modality from the nanomaterial used, through the mechanism that generates or amplifies the signal, to the biomarker detected and the performance reported. Gold-outlined boxes give the quantitative metrics from the included sources, such as a 0.2 pg/mL limit of detection for CYFRA 21-1 and 84%–89% clinical sensitivity for CTC capture. Values are transcribed as reported and mostly reflect analytical rather than population-level validation. Data from Table 2.

Figure 4. Strategies that govern nanocarrier localisation and payload release. (A) Passive targeting: long-circulating carriers cross 100–700 nm fenestrations in leaky tumour vessels and are retained because lymphatic drainage is impaired; PEGylation slows clearance. (B) Active targeting: ligands (antibodies, aptamers, RGD, folate) bind overexpressed receptors (EGFR, HER2, folate receptor, integrin αvβ3) and trigger endocytosis. (C) Stimuli-responsive release: endogenous cues (acidic pH, glutathione, MMPs) or external inputs (NIR light, magnetic field, ultrasound, heat) trigger site-specific release. Based on Sections 2.3 and 4.2.

diluted serum (Deshwal et al., 2024; Kumar et al., 2021). If such performance holds outside the laboratory, the implications for early lung cancer detection could be considerable.

4.3.3 Liquid Biopsy and Multimodal Imaging

Liquid biopsy is perhaps the diagnostic area closest to clinical practice. NanoVelcro silicon-nanowire substrates and electrokinetic microfluidic chips capture CTCs and exosomes (glypican-1, CD63) from whole blood with reported clinical sensitivities of 84%–89% (Jayaraman et al., 2021; Kumar et al., 2021; Morris et al., 2014) (Table 2). Triple-modality gold–gadolinium–Raman silica nanoparticles push in a different direction, combining MRI, photoacoustic and SERS imaging in one construct for intraoperative definition of brain tumour margins (Jayaraman et al., 2021; Morris et al., 2014). The trend across these studies is towards multimodality, but the number of platforms tested in humans remains small.

4.4 Multifunctional Theranostics, Catalytic Nanozymes and TME Remodelling

4.4.1 Phototherapies

Theranostic platforms integrate imaging and therapy so that drug accumulation and response can be followed in real time (Deswal et al., 2021; Pardeshi & Souto, 2019) (Table 3; Figure 5). In PTT, gold nanorods, graphene oxide and polydopamine-coated nanoMOFs heat tissue above 42 °C under NIR irradiation, which disrupts tumour vasculature and dense collagen and seems to improve the penetration of co-delivered drugs (Ammar et al., 2025; Ding et al., 2022; Gharpure et al., 2015). PDT platforms such as porphyrinic Zr-MOFs and chlorin e6-loaded silica nanoparticles generate ¹O₂ on irradiation (Ammar et al., 2025; Deshwal et al., 2024; Ding et al., 2022). Evidence for both modalities is extensive in rodent melanoma, breast and brain tumour models; clinical data are largely limited to gold nanoshells (Ammar et al., 2025; Gharpure et al., 2015).

4.4.2 Catalytic and Sonodynamic Strategies

Nanozymes based on iron oxide, cerium oxide or metal–organic frameworks mimic peroxidase, catalase, oxidase and superoxide dismutase (Deshwal et al., 2024; Yuan et al., 2026). In CDT, Fe- and Cu-based MOFs, PtPd/MnCo–CeO₂ and m-Cu₉S₅ nanozymes convert endogenous H₂O₂ into •OH while consuming GSH, so that oxidative stress is amplified selectively in the acidic tumour milieu (Deshwal et al., 2024; Deswal et al., 2021). SDT platforms such as PCN-224/Pt MOFs and PEGylated TiO₁₊ₓ nanorods reach tumours more than 10 cm deep, and some release nitric oxide that suppresses protective autophagy (Deshwal et al., 2024). These approaches are still almost entirely preclinical.

4.4.3 Hypoxia Relief and Immunomodulation

Catalase-mimicking nanozymes such as MnZ@Au and Ru nanoclusters decompose intratumoural H₂O₂ into O₂, which relieves hypoxic resistance and enhances PDT and radiotherapy (Deshwal et al., 2024; Ding et al., 2022) (Table 3). Ferumoxytol, already approved by the FDA for iron replacement, appears to reprogram TAMs from M2 to M1. This could convert immunologically "cold" tumours into T-cell-infiltrated "hot" ones (Chakraborty et al., 2025; Deswal et al., 2021). The repurposing of an approved agent is attractive, but most of the immunological evidence is still mechanistic.

4.5 Regenerative Biomaterials, Bioprinting and Stem Cell Guidance

4.5.1 Nanofibrous and Mineral-Reinforced Scaffolds

In regenerative medicine, nanomaterials reproduce the structural and biochemical complexity of the native ECM in order to direct adhesion, proliferation and lineage commitment (Chakraborty et al., 2025; Jayabal, 2025) (Table 4; Figure 6). Electrospun PCL, PLA, PLGA and silk-fibroin fibres mimic collagen fibrils, promoting fibroblast migration in wound healing and guiding axonal regrowth in nerve repair (Jayabal, 2025; Shi et al., 2010). Nanominerals such as nHA, bioactive glass, Laponite® nanosilicates and cerium oxide strengthen hydrogels, and the Ca²⁺, PO₄³⁻ and Si⁴⁺ ions they release drive osteogenic differentiation without exogenous growth factors (Chakraborty et al., 2025; Jayabal, 2025). Cerium oxide nanoparticles additionally scavenge ROS, which may protect transplanted stem cells from oxidative damage (Chakraborty et al., 2025).

4.5.2 Conductive Composites and Bio-Inks

CNT- and GO-containing hydrogels provide electrical conductivity that guides neurogenesis and synchronises cardiomyocyte contraction (Jayabal, 2025; Kazemi et al., 2024). Nanomaterial additives in bio-inks improve shear-thinning, shape fidelity and cell viability, which is reported to exceed 90%. Four-dimensional constructs built from stimuli-responsive nanocomposites can change geometry over time (Chakraborty et al., 2025; Jayabal, 2025). As Figure 6 suggests, polymer nanofibres are the most widely used strategy, found in five of the six tissue domains examined, whereas conductive and factor-releasing systems remain confined to neural and vascular niches. Most of this evidence comes from in vitro and small-animal studies.

5. Reconciling Preclinical Promise with Clinical Reality in Nanomedicine

5.1 Principal Findings

This review set out to examine four domains of medical nanotechnology within one frame, and the picture that emerges is one of shared principles but uneven maturity. A small set of nanoscale properties, namely high surface-area-to-volume ratios, tunable surfaces, size congruence with biomolecules and, for some materials, optical or magnetic behaviour, recurs across diagnostics, drug delivery, oncology and regeneration (Figure 1). These properties seem to explain most of the reported gains. Clinical validation, however, is concentrated in a few places: liposomal and lipid-nanoparticle drugs, iron oxide agents and, to a lesser degree, liquid-biopsy devices (Tables 1–3). Elsewhere, and particularly for nanozymes, sonodynamic platforms and 4D bio-inks, the evidence is still almost entirely preclinical. It would be easy to read the breadth of the literature as a sign of readiness. That reading is probably premature.

5.2 Drug Delivery and the EPR Debate

5.2.1 How Reliable Is Passive Targeting?

Tumour targeting has long been regarded as the classical testing ground of nanomedicine (Lepeltier et al., 2015), and the EPR effect has been its main conceptual support. The corpus confirms that most carrier classes fall within the 100–700 nm fenestration window (Figure 2), and that PEGylation and particle geometry can improve circulation and extravasation (Alexis et al., 2008; Bamrungsap et al., 2012). Yet the same sources acknowledge that vascular permeability varies widely between patients and tumour types (Deswal et al., 2021; Gopi et al., 2021; Morris et al., 2014). This is not a minor caveat. If EPR is weak in a given tumour, a carrier designed around it may accumulate little more than the free drug, and the clinical benefit may shrink to reduced toxicity alone, which is valuable but more modest than often claimed. The success of Doxil® arguably illustrates exactly this: its main advantage lies in lower cardiotoxicity rather than dramatically better efficacy (Bamrungsap et al., 2012; Jayaraman et al., 2021).

5.2.2 Active Targeting and Smart Carriers

Active targeting and stimuli-responsive release are usually presented as remedies (Jain et al., 2005; Singh, 2025), and mechanistically they are persuasive (Figure 4). Still, a ligand can only bind its receptor once the particle has reached the tissue, so active targeting refines distribution within a tumour more than it overcomes poor delivery to it. Added surface complexity also makes manufacture harder (Ding et al., 2022; Kazemi et al., 2024). Lipid nanoparticles, perhaps the most successful recent platform, are comparatively simple in design (Wacker, 2019). This may suggest that simplicity, rather than maximal functionality, is what tends to survive translation.

5.3 Diagnostics: Analytical Sensitivity Versus Clinical Utility

The diagnostic findings are impressive on paper: picogram-per-millilitre detection by SERS, a 0.2 pg/mL limit of detection for CYFRA 21-1 and roughly 30-fold brighter QD signals (Deshwal et al., 2024; Kumar et al., 2021) (Table 2; Figure 3). Analytical sensitivity, however, is not the same as clinical usefulness. A test that detects a biomarker at vanishingly low levels can also detect it in people who will never develop disease, and false positives carry their own costs. The 84%–89% sensitivity reported for nanostructured CTC capture (Kumar et al., 2021; Morris et al., 2014) is more informative precisely because it was measured clinically, although specificity and the characteristics of the patient population matter as much as the headline figure. The cadmium content of some QDs is a further, and often under-discussed, concern for use in vivo. SPIONs, by contrast, have a clearer safety record, and their use as gadolinium-free contrast agents seems a more immediate opportunity (Azmi & Elgharbawy, 2021; Singh, 2025).

5.4 Theranostics and the Tumour Microenvironment

5.4.1 Promise of Combined Modalities

Theranostic and TME-directed strategies are among the most inventive in the field (Table 3; Figure 5). Combining catalase-like oxygen generation with PDT, or Fenton chemistry with GSH depletion, tackles the very features of tumours, namely hypoxia and antioxidant defence, that make them resistant to conventional therapy

Figure 5. Nanotheranostic modalities acting on the tumour microenvironment. The central ellipse summarises the hostile features of the TME, including hypoxia, acidic pH, excess H₂O₂, high glutathione and M2-polarised macrophages. Six surrounding boxes show nanoplatform-based modalities, each with representative nanosystems and its core reaction or effect. The dashed arrow marks the synergy by which oxygen from catalase-like nanozymes enhances photodynamic therapy, and imaging guidance (top) allows treatment to be monitored in real time. Data from Table 3.

Figure 6. Matrix of nanomaterial strategies against target tissues in regenerative medicine. Rows list seven nanomaterial strategies and columns six tissue domains. A large filled circle means the included sources report that strategy in that domain; a small grey dot means none was reported. Polymer nanofibres appear in five of six domains, whereas carbon nanomaterials and factor-loaded fibres are confined to neural and vascular uses, and stimuli-responsive nanocomposites to 4D bio-inks. The matrix reflects reporting frequency in the corpus, not comparative efficacy. Derived from Table 4.

(Deshwal et al., 2024; Deswal et al., 2021). The repurposing of ferumoxytol to repolarise macrophages is particularly interesting because it begins from an approved, characterised agent (Chakraborty et al., 2025; Deswal et al., 2021).

5.4.2 Complexity as a Barrier

There is, though, a tension here. Each added function, whether imaging, catalysis, photothermal conversion or immune modulation, adds a component that must be manufactured reproducibly, characterised and shown to be safe. Nanozyme activity, for example, may be hard to confine to the tumour; redox chemistry that damages cancer cells could plausibly harm healthy tissue where H₂O₂ and pH conditions overlap (Deshwal et al., 2024; Yuan et al., 2026). The multimodal platforms in Table 3 are almost all at proof-of-concept stage (Deswal et al., 2021; Ding et al., 2022). Regulators will need to judge them as combination products, and it is not obvious that existing frameworks are ready to do so (Ammar et al., 2025; Rana & Bhatnagar, 2021).

5.5 Regenerative Nanomaterials: Biomimicry with Limited Clinical Data

Regenerative applications show how closely nanomaterials can imitate native tissue: nanofibres that resemble collagen, minerals that release osteoinductive ions and conductive fillers that support electrically active cells (Chakraborty et al., 2025; Jayabal, 2025) (Table 4; Figure 6). The matrix in Figure 6 makes one pattern visible. Polymer nanofibres are used almost everywhere, while other strategies are specialised by tissue. Whether this reflects true biological fit or simply the maturity and accessibility of electrospinning is difficult to say from the present literature. Reported cell viabilities above 90% for nano-reinforced bio-inks are encouraging (Jayabal, 2025), but long-term in vivo integration, degradation and the fate of non-degradable fillers such as CNTs remain largely unknown (Chakraborty et al., 2025; Jayabal, 2025). Nanozymes for bone regeneration (Yuan et al., 2026) point to a possible convergence between oncology and regeneration, an overlap that might be worth pursuing deliberately.

5.6 Cross-Cutting Translational Barriers

5.6.1 Nanotoxicology and Clearance

Four barriers recur across every domain (Figure 1). The first is safety. Long-term accumulation, oxidative stress, immune activation and organ toxicity are cited repeatedly as concerns, especially for non-biodegradable materials (Ammar et al., 2025; Chakraborty et al., 2025; Jayabal, 2025; Jayaraman et al., 2021). Many studies report short-term biocompatibility; far fewer follow particle fate over months.

5.6.2 Manufacturing and Biological Heterogeneity

The second barrier is manufacturing. Reproducing size distribution, drug loading and ligand density from batch to batch is difficult for complex constructs, and nanoMOFs in particular show batch-dependent behaviour (Chakraborty et al., 2025; Ding et al., 2022; Jayabal, 2025; Morris et al., 2014). The third is biological heterogeneity, most clearly visible in EPR variability, but likely also relevant to protein-corona formation and immune responses that differ between individuals (Deswal et al., 2021; Gopi et al., 2021; Singh, 2025).

5.6.3 Regulation and Standardisation

The fourth barrier is regulatory. Standardised characterisation protocols, validated toxicity assays and clear guidance for nanoscale products are still lacking (Ammar et al., 2025; Chakraborty et al., 2025; Jayabal, 2025). Without them, it is difficult even to compare results between laboratories, let alone to bring products through approval.

5.7 Future Directions

Several developments may help. Green synthesis using plant extracts or microorganisms could reduce toxic reagents and possibly improve biocompatibility (Ammar et al., 2025; Azmi & Elgharbawy, 2021). Biomimetic cell-membrane camouflage may extend circulation and reduce immune recognition (Ammar et al., 2025; Rana & Bhatnagar, 2021). Artificial intelligence-guided design could help navigate the large parameter space of size, shape, charge and composition more efficiently than trial and error (Ding et al., 2022; Jayabal, 2025). Perhaps most important, though less glamorous, is the development of shared standards for reporting particle characterisation and long-term safety, without which progress in the other areas will be hard to judge. Patient stratification, for instance selecting patients by imaging evidence of EPR before giving an EPR-dependent drug, could also allow existing platforms to be used more effectively (Morris et al., 2014; Pardeshi & Souto, 2019).

5.8 Strengths and Limitations of This study

This review has some strengths. It covers four domains within one framework, charts quantitative performance systematically and links its tables directly to its figures. It also has limitations that should be stated plainly. As a narrative review, it does not pool data statistically and cannot estimate effect sizes. The corpus of 28 sources is modest, contains many secondary reviews and book chapters and relies heavily on preclinical evidence, so some reported values may have been carried from source to source without independent confirmation. Restriction to English-language publications may have omitted relevant work. Finally, the field moves quickly, and some recent clinical results may not yet be reflected. Systematic reviews with formal risk-of-bias assessment, focused on single platforms with clinical data, would be a natural next step.

6. Conclusion

Nanotechnology has given medicine tools that work at the scale of its molecular targets. This review shows that a small set of nanoscale properties supports advances across diagnostics, drug delivery, oncology and regenerative therapy, from picogram-level biomarker detection and liposomal drugs with lower cardiotoxicity to tumour-microenvironment remodelling and scaffolds that mimic the native matrix. The evidence is uneven, though. Lipid carriers, iron oxide agents and liquid-biopsy devices have clinical support, whereas nanozymes, sonodynamic platforms and 4D bio-inks remain mostly preclinical. Variable EPR, uncertain long-term toxicity, difficult scale-up and immature regulation limit translation in every domain. Because the domains share design principles, however, solutions developed in one area may well transfer to the others. Progress will probably depend less on adding functions to individual particles than on standardised characterisation, longer-term safety studies, reproducible manufacturing and patient stratification. If these foundations are built, nanomedicine may move from impressive prototypes to dependable, personalised clinical practice.

References