The cardiotoxicity of doxorubicin significantly restricts its effectiveness, even though it remains a crucial element of breast cancer chemotherapy. Nifedipine (NFP) offers multi-mechanistic therapeutic benefits, including vasodilation, anti-proliferative activities, suppression of cellular apoptosis, and potent anti-inflammatory and antioxidant properties. However, the translation of oral NFP into an effective cardioprotective adjuvant is hindered by its poor solubility, first-pass hepatic metabolism, and poor bioavailability. Hence, this study aimed to develop a nasal NFP-loaded ufasomes (NLU) spray formulation to enhance the permeation, bioavailability, sustained release, and cardiac accumulation of NFP when co-administered with doxorubicin. Various NLU formulations were developed and optimized employing Design-Expert® software. The in vivo cardioprotective efficacy of the nasal NLU was comprehensively evaluated in a doxorubicin-induced cardiotoxicity rat model. The optimal NLU substantially prolonged drug sustainability and amplified mucosal permeability by 69.07% and 6.47-fold, respectively, compared to the free NFP suspension. Furthermore, nasal NLU formulation achieved a remarkable 7.33-fold enhancement in bioavailability and a 5.40-fold increase in cardiac tissue accumulation when contrasted with conventional oral NFP administration. Furthermore, the nasal NLU spray exhibited superior cardioprotective and antioxidant performance over the oral NFP. In conclusion, these findings establish the nasal NLU formulation as a promising therapeutic platform to mitigate doxorubicin-induced cardiotoxicity.
Resolution of inflammation is an active, tightly regulated process, and its dysregulation contributes to acute and chronic inflammatory diseases. This study investigated the anti-inflammatory and pro-resolving effects of Rosa damascena-derived nanovesicles (RD-NVs), with particular emphasis on efferocytosis. RD-NVs were isolated by ultracentrifugation and characterized using dynamic light scattering, nanoparticle tracking analysis, zeta potential analysis, and electron microscopy. The nanoparticles exhibited spherical morphology, an average diameter of approximately 212 nm, and a zeta potential of approximately -40 mV, indicating good colloidal stability. RD-NVs were biocompatible with RAW264.7 macrophages and significantly reduced intracellular reactive oxygen species (68.48% and 41.18%) while restoring mitochondrial membrane potential (90.80% and 93.82%) in LPS-stimulated cells. They also downregulated TNF-α and HMGB1 expression while restoring GAS6 expression in a dose-dependent manner, supporting enhanced efferocytosis and inflammation resolution. Western blotting confirmed GAS6 restoration, and reduced HMGB1 suggested diminished secondary necrosis. Biodistribution studies showed preferential accumulation in the liver and spleen. In vivo, RD-NVs significantly attenuated LPS-induced paw edema, reduced leukocyte infiltration, and suppressed TNF-α expression. These findings demonstrate that RD-NVs promote inflammation resolution through restoration of GAS6-associated efferocytosis, mitochondrial protection, and suppression of inflammatory mediators, highlighting their potential as plant-derived resolution-oriented nanotherapeutics.
Silk fibroin (SF) and silk sericin (SS) are promising biomaterials for lung cancer drug delivery because of their biocompatibility, biodegradability, and versatile processing. SF-based systems can provide structural stability and controlled or prolonged release, although release behavior depends on drug properties, loading strategy, secondary structure, and formulation architecture. Engineered SS-containing systems may contribute hydrophilicity, formulation-dependent environmental responsiveness, and biologically relevant interactions, but SS-rich formulations can show limited structural robustness. This review compares representative SF-based, SS-based, and SS/SF composite systems, focusing on pulmonary targeting, responsive drug release, tumor-microenvironment interactions, and translational considerations. Selected SS/SF composites have demonstrated combinations of geometry-associated pulmonary accumulation, environment-associated release, prolonged local retention, and immune- or tumor-microenvironment-related activity. However, evidence for SF/SS complementarity remains limited and heterogeneous, with major differences in silk source, processing, composition, cargo, administration route, and disease model. Accordingly, this complementarity should be regarded as a provisional conceptual framework rather than a universally validated mechanism. Future progress requires standardized materials, composition-matched comparisons, formulation-specific safety assessment, reproducible manufacturing, and clinically relevant delivery strategies to determine whether SS/SF composites provide measurable advantages over simpler silk-based or non-silk systems.
Carrier-free nanoparticles have emerged as a promising class of nanomedicines for cancer therapy, characterised by ultrahigh drug-loading capacity, reduced dependence on inert carriers, and enhanced therapeutic efficiency. Diverse design strategies, including molecular self-assembly, covalent prodrug conjugation, and stimuli-responsive construction, have enabled the development of structurally versatile and functionally integrated carrier-free nanoplatforms. These systems exhibit improved physicochemical properties, enhanced tumour accumulation, and multifunctional therapeutic capabilities. However, existing reviews have mainly focused on specific assembly strategies or individual therapeutic applications, while a systematic understanding linking nanoparticle design, tumour-specific responses, and clinical translation remains insufficient. This review summarises recent advances in the design and fabrication of carrier-free nanoparticles and provides an integrated analysis of their assembly mechanisms, physicochemical characteristics, and therapeutic applications across diverse cancer types, including breast, lung, and liver cancers. In addition, this review comparatively discusses different therapeutic modalities, including chemotherapy, photothermal therapy, photodynamic therapy, chemodynamic therapy, ferroptosis, and immunotherapy, with emphasis on their advantages, limitations, and translational potential. Current clinical progress, patent trends, and future challenges are also analysed to provide insights into the rational design and clinical development of carrier-free nanoparticles for cancer therapy.
Abemaciclib (AMC) is a selective CDK4/6 inhibitor widely utilised for breast cancer therapy; however, its efficacy is compromised by poor bioavailability and low aqueous solubility. This study aimed to enhance the sustained release, targeting, and efficacy of AMC via developing an intratumoral, in situ pH-responsive AMC-loaded novasome (IPANF) hydrogel. The optimal AMC-novasome was tailored using Design-Expert® software and subsequently incorporated into a chitosan/glyceryl monooleate mixture to develop IPANF. The in vivo anti-tumour efficacy and safety profile of the IPANF were evaluated using an Ehrlich ascites carcinoma model. Within 24 h, the IPANF formulation exhibited a significantly sustained drug release by 65.31% compared to the free AMC suspension. The intratumoral IPANF resulted in a profound 96.08% reduction in tumour volume, a 70.46% recovery in body weight, and a suppression of the CA 15-3 and CA 27-29 levels by 92.66% and 91.23%, respectively. Notably, a 100% survival rate was observed in the intratumoral IPANF group. Histopathological assessments firmly validated the superior therapeutic efficacy of the intratumoral IPANF hydrogel. Furthermore, the intratumoral IPANF formulation demonstrated an excellent safety profile. These findings underscore the clinical potential of the intratumoral IPANF hydrogel as a highly efficient, localised, and safe platform for advanced breast cancer treatment.
Cancer is among the leading causes of death globally. Early diagnosis and therapy provide cancer patients with the highest chance of survival. Despite recent significant advances in understanding the complex pathways that contribute to cancer progression and metastasis, researchers are still unable to adequately treat cancer progressing to many crucial organs. As cancer cells and tumour microenvironments are highly complex, the mechanisms of tumour invasion, tumour development, and metastasis remain incompletely understood. Therefore, to grasp the complex molecular information behind biological behaviour of tumours, novel technologies for cancer detection and real-time observation are urgently needed. Quantum dots (QDs) are indeed luminous semiconductor materials in the nanometric size range. Considering their unique optical traits including excellent luminescence, simultaneous acquisition of numerous signals, stability over time, and tunable emission spectra, QDs are appealing as possible cancer theranostic devices. Zinc sulphide (ZnS) QDs are frequently employed as a cornerstone for precision onco-targeting owing to their high quantum yield, low toxicity, biocompatibility, and versatility for diverse surface modifications. ZnS QDs are now showing great promise for cancer bioimaging and anticancer drug delivery. The present review describes the frontiers of surface modifications and theranostic applications of ZnS QDs in the treatment of various cancers.
TRAIL is a potent anticancer protein that selectively reduces the viability of malignant cells but is limited clinically by its short half-life. This study developed novel TRAIL-loaded drug carrier systems to prolong its mean residence time, consequently enhance its biological activity and enhance therapeutic efficacy in breast cancer, and evaluate tumour targeting and modulation of apoptotic and autophagic pathways in vitro and in vivo. TRAIL-loaded carrier systems were prepared using PLGA/Gelucire 48/16 nanoparticles and exosome-based formulations. Following physicochemical characterisation, biological effects were assessed in MDA-MB-231 cells and an EAC mouse tumour model, with cellular responses analysed by flow cytometry and qPCR. Histopathological assessments included HE staining, TUNEL assay, and Ki-67 IHC. Both formulations significantly suppressed cell viability and enhanced apoptosis in MDA-MB-231 cells. Treatment with these carrier systems upregulated the expression of Caspase-3 and LC3B genes in-vitro and in mouse tumour tissues, indicating activation of apoptotic and autophagic pathways. In the EAC tumour model, TRAIL-loaded formulations reduced tumour growth, decreased the Ki-67 proliferation index, and induced marked tumour regression. Encapsulation of TRAIL in PLGA/Gelucire 48/16 or exosome-based carriers enhances its stability and antitumor activity, highlighting the potential of these carrier platforms to improve TRAIL-encapsulated biotechnological therapeutics for breast cancer treatment.
The uncontrolled proliferation of abnormal skin cells is the hallmark of skin carcinoma. Sonidegib (SDB), a potent Hedgehog pathway inhibitor, is clinically approved for the treatment of skin carcinoma. However, its therapeutic utility is restricted by poor bioavailability, high hydrophobicity, and significant systemic adverse effects. This study aimed to develop an intratumor SDB-loaded transbilosomes (SLT) formulation to improve localised therapeutic efficacy and mitigate systemic toxicity. Several SLT formulations were developed and optimised using Design-Expert® software. The optimised SLT formulation was evaluated for safety, intratumor retention, and efficacy using a DMBA-induced skin carcinoma rat model. Results demonstrated that the optimal SLT formulation achieved a 68.87% reduction in drug release after 24 h compared to free SDB. Pharmacokinetic evaluation revealed a 7.78-fold increase in relative systemic bioavailability compared to oral SDB. In vivo efficacy studies showed an 84.22% reduction in tumour volume in the intratumor SLT-treated group, with no observed fatalities compared to the oral SDB. Histopathological and safety assessments confirmed the significant antiproliferative effects and the favourable preliminary safety profile of the intratumor SLT formulation. These findings suggest that the intratumor SLT formulation provides an effective option for the management of skin carcinoma.
The Zika virus (ZIKV), a neurotropic flavivirus, poses a global health threat with no approved antivirals. Curcumin, a natural polyphenol, exhibits potent antiviral properties but suffers from poor bioavailability. This study developed Curcumin-loaded Solid Lipid Nanoparticles (CUR-SLNs) to overcome these limitations. A 32 factorial design optimized SLNs using glyceryl monostearate. The lead formulation (CUR-SLN6) exhibited a particle size of 53.25 nm, high entrapment efficiency (93.2%), and sustained release (52.89% over 24 h). In Wistar rats, CUR-SLNs demonstrated a 15-fold increase in oral bioavailability and significant brain biodistribution. In Vero cells, CUR-SLNs exhibited 90% reduction in ZIKV plaque formation (IC50 = 2.5 µM), ten times more potent than native curcumin. Mechanistic studies revealed inhibition of viral entry and a 3-log reduction in viral RNA replication. Histopathological analysis in a lethal AG129 mouse model showed CUR-SLN6 provided marked neuroprotection against ZIKV-induced necrosis and inflammation, with efficacy comparable to Sofosbuvir. No systemic toxicity was observed. The method demonstrated excellent greenness (AGREE score 0.86) and whiteness (RGB score 90). This first demonstration of SLN-based curcumin delivery with enhanced bioavailability, brain targeting, and neuroprotective efficacy highlights its clinical potential as an oral neurotherapeutic agent.
The therapeutic potential of tectoridin for melasma treatment is limited by its poor aqueous solubility. To address this limitation, we developed tectoridin-loaded ethosomes using the film dispersion method, and optimised the formulation via orthogonal design, before incorporation of these ethosomes into a gel. The optimised tectoridin ethosomes showed a spherical morphology with uniform dispersion, a particle size of 197.84 ± 1.43 nm, a zeta potential of -22.75 ± 0.61 mV, a polydispersity index of 0.209 ± 0.05, an encapsulation efficiency of 92.82 ± 0.16%, and a drug loading of 9.75 ± 0.05%, thereby demonstrating good storage stability for 30 days at both 4 °C and 25 °C. The resulting Tectoridin (Te)-Ethosomes-Loaded Thermosensitive Gel (Te-ethosomes@Gel) exhibited suitable rheological properties, erosion rate and in vitro release profile. Both ethosomes and the gel enhanced drug release, cellular uptake and safety. All tectoridin formulations significantly inhibited tyrosinase activity, reduced melanin content and deposition in PIG1 cells and suppressed the expression of transcription of tyrosinase, TRP1, MITF, Myosin Va, Rab27a, Cdc42, p-p38 and p-ERK proteins. In vivo pharmacodynamic studies in a rat model of melasma further demonstrated that the Te-ethosomes@Gel significantly improved skin pigmentation, reduced oxidative stress markers and restored normal skin histology, with effects superior to those of free tectoridin or ethosomes alone. These findings demonstrate that Te-ethosomes@Gel offers a promising novel strategy for treating melasma.
Acute liver injury (ALI) is a syndrome characterised by rapid deterioration of liver function, rapid progression, and high mortality. In this study, a liver-targeted drug delivery system, galactosylated chitosan modified Coreopsis tinctoria flavonoid liposome (GC-CTF-Lip) was constructed. The targeted ligand was synthesised by the amidation reaction between chitosan and lactobionic acid, and its structure was identified. The modification conditions of GC on liposomes were optimised and characterisation of liposomes was studied. The liver-targeting ability of GC-CTF-Lip was evaluated through in vivo and in vitro experiments. A mouse model of ALI induced by CCl4 was established to evaluate the hepatoprotective effect of GC-CTF-Lip. The results confirmed that lactobionic acid was successfully grafted onto chitosan. Finally, GC-CTF-Lip with particle size of 236.32 ± 0.60 nm and encapsulation efficiency of 68.67 ± 0.58% was obtained. GC-CTF-Lip improved the uptake efficiency of CTF in hepatocytes in vitro and exhibited excellent liver enrichment in vivo. Serum ALT/AST levels were significantly decreased, and the histological liver injury was alleviated. It exhibited a trend of liver enrichment and a hepatoprotective effect. This liver-targeted nanodrug delivery system can achieve active accumulation of drugs at the lesion site, providing a potential strategy for the prevention of ALI.
Drug repurposing can accelerate oncology translation by leveraging approved compounds with known pharmacology; success depends on a plausible mechanism for the new indication. The microtubule cytoskeleton is a validated anticancer target, yet tubulin-directed activity is often overlooked for non-oncology drugs. Using nanoDSF, FDA-approved compounds were recently screened for effects on tubulin polymerisation, identifying multiple previously unrecognised microtubule-targeting agents (MTA) including Auranofin, Ebselen, Riboflavin, Aprepitant, Benzarone and Nifedipine derivatives, etc. Many hits match reported microtubule perturbation or cancer-relevant phenotypes, and several have been considered for oncology repositioning. These observations suggest microtubule targeting may contribute to anticancer effects more often than appreciated and that tubulin remains an underexploited repurposing target. The aim of this review is to place these newly identified MTAs in the context of current knowledge and to discuss their potential for drug repurposing in oncology.
Conventional ulcerative colitis (UC) therapies suffer from limited efficacy and toxicity. Although physcion (PHY) has multi-target anti-inflammatory activity, its poor solubility and lack of targeting restrict clinical use. To overcome these issues, we developed folate receptor (FR)-targeted DSPE-PEG liposomes encapsulating PHY using thin-film hydration and central composite design optimization. The resulting liposomes showed uniform size (approximately 160 nm, PDI < 0.18), high entrapment efficiency (>92%), and good stability. In vitro release was significantly improved, and cellular uptake was enhanced in inflammatory EC cells via FR-mediated endocytosis. Pharmacokinetic studies revealed prolonged half-life and increased bioavailability, while tissue distribution confirmed colon-specific enrichment. In DSS-induced UC mice, targeted liposomes repaired colonic mucosa, reduced fibrosis, suppressed pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and alleviated oxidative stress through coordinated NF-κB/Nrf2 regulation, with efficacy superior to conventional liposomes and positive controls. Safety assessments showed no notable cytotoxicity to normal cells. This work offers a promising FR-targeted nanocarrier to overcome PHY's clinical limitations and provides a foundation for targeted UC therapy.
Breast cancer remains one of the most prevalent causes of cancer deaths globally. This is because systemic toxicity, multidrug resistance and poor tumour selectivity typically make treatment less effective. Traditional drug delivery methods depend heavily on passive targeting and diffusion-controlled release. Enzyme-responsive drug delivery systems have recently been developed as a biologically precise approach that takes clinical advantage of the specialised enzymatic environment of breast tumours, such as the overproduction of matrix metalloproteinases, cathepsins and hyaluronidase. Among advanced nanocarriers, two-dimensional (2D) nanomaterials have attracted significant attention because of their high surface-to-volume ratio, ultrathin planar structure, tuneable surface chemistry, and exceptional drug-loading capacity. Graphene derivatives, black phosphorus, layered double hydroxides, transition metal dichalcogenides, and MXenes are all examples of materials that can be used to make enzyme-cleavable linkers. This paper critically discusses the enzymatic characteristics of the breast tumour microenvironment, design principles of enzyme-responsive linkers, classifications and physicochemical properties of 2D nanomaterials and their functionalization strategies. Furthermore, toxicity considerations, preclinical advancements, translational barriers, and future perspectives are analysed. Collectively, enzyme-responsive 2D nanomaterials represent a promising next-generation approach for precision breast cancer therapy, offering improved targeting efficiency, controlled drug activation, and potential theranostic integration.
Molecular engineering, chemical biology and translational oncology have transformed the landscape of targeted cancer therapies. Antibody-drug conjugates (ADCs) have advanced into clinically validated platforms that combine antigen-specific recognition with potent cytotoxic payloads, supported by innovations in linker chemistry, drug-to-antibody ratio (DAR) optimisation, and bispecific or multispecific antigen targeting. Parallel to ADC development, targeted protein degradation (TPD) technologies - proteolysis-targeting chimaeras (PROTACs), molecular glues, and emerging lysosomal and autophagy-based degraders enable the catalytic elimination of oncogenic drivers that were previously considered undruggable. Nanomedicine-based delivery enhances therapeutic selectivity, improves pharmacokinetics and overcomes barriers to intracellular drug transport. Rational combination therapies that integrate these platforms with immune checkpoint inhibitors, kinase inhibitors and tumour microenvironment (TME)-modulating agents address tumour heterogeneity and adaptive resistance more effectively than monotherapies. This review synthesises the foundations of ADCs, multispecific antibodies, protein degraders, nanomedicine platforms, targeted small-molecule inhibitors and their combination strategies. Clinically, the convergence of these modalities promises to extend durable responses to patient populations with refractory, molecularly complex malignancies by enabling individualised, mechanism-driven therapeutic selection.
Eletriptan hydrobromide (EHBr) exhibits poor oral bioavailability due to extensive first-pass metabolism by CYP3A4 and P-glycoprotein-mediated efflux at the blood-brain barrier. Therefore, this study was conceptualised to encapsulate EHBr into solid lipid nanoparticles (SLNs) and deliver them via a transdermal microneedle (MN) array for targeted brain delivery. SLNs were formulated using a lipid matrix comprising glyceryl monostearate, stearic acid and hydrogenated soy phosphatidylcholine, with Poloxamer-188 as the emulsifier. The optimised SLNs showed a particle size of 165.5 ± 71.75 nm, zeta potential of -27.1 ± 4.48 mV and entrapment efficiency of 63.25 ± 1.44%, and were incorporated into polymer-based MNs. The optimised MNs exhibited high drug content (93.65 ± 1.39%), good mechanical strength (p < 0.05), excellent insertion efficiency (F = 17.83, p = 3.03 × 10-8) and rapid in situ dissolution. Ex vivo studies demonstrated sustained EHBr release (89.67 ± 1.03% over 24 h), following first-order kinetics (R2 = 0.998) with non-Fickian diffusion (n = 0.79). FTIR and XRD analyses confirmed drug excipient compatibility and formulation stability. In vivo evaluation in Wistar rats revealed significant antinociceptive, anxiolytic and anti-photophobic effects (p ≤ 0.027), and reduced neurogenic inflammation, confirming the enhanced brain delivery and bioavailability of EHBr.
Subcellular organelle targeting is changing the way nanomedicine is designed, moving the field beyond simple cellular entry towards more precise intracellular localization, controlled cargo release, and functional activity within disease-relevant compartments. This review critically discusses nanomaterial-based strategies for targeting the nucleus, mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus, and cytoskeleton-associated trafficking pathways. Its main novelty is the use of a cross-organelle, mechanism-based framework that links nanocarrier physicochemical properties with intracellular transport biology, rather than examining each organelle or delivery platform separately. Nanocarriers are compared according to their targeting mechanisms, cargo compatibility, therapeutic potential, and translational limitations. Particular attention is given to nuclear import mediated by NLS-, CPP/TAT-, and aptamer-based strategies; mitochondrial delivery shaped by membrane potential, membrane fusion, and redox-responsive release; lysosomal targeting for pH- and enzyme-activated therapies; and ER/Golgi-directed delivery through retrograde trafficking, retention motifs, and modulation of stress-related pathways. The review also focus on stimuli-responsive release, biomimetic surface engineering, extracellular vesicle scalability, CRISPR/Cas delivery, base and prime editing, and targeted protein degradation, all of which may support more programmable forms of intracellular therapy. Importantly, it separates true organelle localisation from transient trafficking or non-specific perinuclear accumulation, emphasising the need for stronger and more reliable validation methods.
Gastrointestinal (GI) malignancies are leading causes of global cancer mortality, with advanced stages showing pronounced therapeutic resistance. A key driver of this aggression is the immunosuppressive and acidic tumour microenvironment (TME). This niche is critically regulated by hypoxia-inducible carbonic anhydrase (CA) isoforms IX and XII. These enzymes catalyse extracellular carbon dioxide hydration, acidifying the milieu to promote invasion, metastasis and immune evasion. Pharmacological CA IX/XII inhibition counteracts this by normalising pH, reducing invasiveness and reinvigorating anti-tumour immunity. Oncolytic viruses (OVs) represent a complementary immunotherapeutic modality. Engineered to selectively replicate in tumour cells, OVs induce direct cytolysis and immunogenic cell death, thereby stimulating systemic immunity. However, their efficacy is hindered by the very acidosis sustained by CA activity. This establishes a compelling synergy: CA inhibition alleviates the acidic barrier to enhance OV spread and potency. Conversely, OV-mediated lysis disrupts hypoxic tumour regions, subsequently downregulating CA IX/XII expression and mitigating acidification. This bidirectional, self-reinforcing cycle positions their combination as a rational strategy to dismantle the TME's metabolic and immunological defences. Preclinical evidence supports that this multimodal approach enhances tumour regression, suppresses metastasis and prolongs survival, offering a promising translational paradigm for GI cancers.
The present study aimed to develop and comprehensively evaluate dalfampridine-loaded chitosan nanoparticles (DLM-CSNPs) for enhanced intranasal brain delivery in a cuprizone-induced demyelination model of multiple sclerosis (MS). The optimised nanoparticles were found to have a particle size of 166.5 nm with PDI 0.24, a positive surface charge (Zeta Potential +24.97 mV), and high entrapment efficiency (82%). Ex Vivo Permeation studies demonstrated that the permeation rate of the drug from DLM-CSNPs (902.26 µg/cm2) was significantly higher compared to the drug solution (609.96 µg/cm2). Sub-acute toxicity studies indicated the lack of significant systemic, hepatic, and renal toxicity of the compound after 28 days of repeated intranasal administration, even at a dose of 4 mg/kg. Pharmacokinetic studies indicated the better targeting of the brain by the intranasal route, where the brain Cmax was two-fold higher, brain AUC 0-12 was significantly higher, brain Tmax was significantly lower, and the brain/plasma ratios were significantly higher compared to the oral route. When compared to the traditional oral route of administration, the intranasal DLM-CSNPs treatment has demonstrated improved delivery of the formulation to the central nervous system, functional recovery, decreased neuroinflammation, and neuroprotective effects, suggesting the therapeutic potential of the DLM-CSNPs formulation for the management of multiple sclerosis.
Wound healing is a complex, dynamic and multistep biological process involving haemostasis, inflammation, proliferation and remodelling, which can be severely compromised in chronic, infected, or non-healing wounds. Conventional wound care strategies often suffer from limitations such as poor drug stability, inadequate tissue penetration, frequent dressing changes and a lack of spatiotemporal control over therapeutic release. In recent years, nanotechnology-based drug delivery systems have emerged as promising platforms to overcome these challenges by enabling targeted, controlled and multifunctional therapeutic interventions. This comprehensive review highlights emerging trends in nanotechnology-driven approaches for wound healing, with a focus on their design and therapeutic potential across different stages of wound repair. The review systematically discusses major nanotechnological platforms, including electrospun nanofibers, advanced hydrogel systems, nanocomposites, polymeric micelles and a wide range of inorganic nanoparticles such as silver, gold, copper, silica and titanium dioxide nanoparticles. Additionally, advanced materials such as graphene and scaffold-based systems, including scaffold-integrated nanoparticles and hydrogel-based scaffolds, are critically examined for their roles in promoting angiogenesis, antimicrobial activity, cell migration and tissue regeneration. Ultimately, this review provides valuable insights into future perspectives and research directions, highlighting the need for multifunctional nanoplatforms to advance next-generation wound healing therapies.
