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Department of Pharmaceutics, College of Pharmaceutical Sciences, Govt. Medical College, Thiruvananthapuram, Kerala, India.
The global cancer burden is reaching a critical inflection point, with projections suggesting a 77% increase in new cases by 2050, disproportionately affecting healthcare systems in low- and middle-income countries. Conventional therapeutics, including systemic chemotherapy, are frequently limited by poor bioavailability, lack of selectivity, and the development of multidrug resistance. Nanofibers have emerged as a transformative drug delivery paradigm, offering a high surface area-to-volume ratio, biomimetic structural features, and the capacity for localized, sustained, and stimuli-responsive release of therapeutic agents. Fabrication techniques such as electrospinning and force spinning allow for the creation of sophisticated architectures, including core-sheath nanofibers that enhance drug stability and enable multidrug loading. These platforms support a diverse range of therapeutic strategies, from localized chemotherapy and gene silencing to advanced photothermal and photodynamic therapies. Furthermore, the integration of stimuli-responsive polymers allows for "on-demand" drug release triggered by environmental factors like pH, temperature, or magnetic fields, which can reverse chemoresistance and improve clinical outcomes. Despite these scientific advances, clinical translation is currently hindered by the biological complexity of the tumor microenvironment, manufacturing scale-up limitations, and the absence of harmonized regulatory guidelines. Future progress relies on the convergence of AI-guided design, patient-specific multi-omics, and quality-by-design manufacturing to transition these platforms from proof-of-concept to validated clinical components of next-generation cancer care.
1.1 The Global Oncological Imperative
Cancer is a complex group of diseases marked by uncontrolled cellular growth due to failures in regulatory processes like cell signaling and apoptosis. In 2022, it accounted for 20 million new cases and 9.7 million deaths, with predictions of a 77% increase by 2050, stressing healthcare systems, especially in low- and middle-income countries (LMICs) [1][2]. There are notable disparities, with lung cancer predominantly affecting males and breast cancer affecting females, the latter expected to exceed 3 million cases annually by 2040. A significant proportion of cancer cases and deaths are occurring in LMICs, which face challenges such as late diagnosis and inadequate treatment, resulting in poorer survival rates [3][4].
In India, the cancer situation is acute, with the National Cancer Registry Programme reporting 1,461,427 cases in 2022, predominantly affecting females (749,251 cases). By 2025, cases are anticipated to rise by 12.8% from 2020 figures, with leading cancers including those of the digestive system, breast, and genital system. Tobacco use remains a significant risk factor, responsible for approximately 33.3% of cancers, escalating to 48.7% among males. Pathogenic infections are also implicated in around 25% of cancer cases in LMICs. This multifaceted landscape necessitates enhanced focus on prevention, early detection, and treatment accessibility [5].
1.2 Limitations of Conventional Therapeutics [6]
Despite advances in surgery and immunotherapy, traditional cancer treatments are still hampered by fundamental biological and chemical hurdles.
Drawbacks of chemotherapy:
Conventional chemotherapeutic drugs are non-specific small molecules that cannot distinguish between healthy and cancerous cells.
This non-selectivity leads to severe side effects such as:
These shortcomings have driven global interest in nanotechnology-based drug delivery system.
1.3 Nanofibers: A Paradigm Shift in Drug Delivery
Nanofibers are redefining drug delivery by offering more precise, localized, and controlled release of therapeutics. Compared to traditional approaches, electrospun nanofibers provide a large surface area, customizable architecture, and the ability to carry a wide range of therapeutic agents, improving drug stability, targeting, and bioavailability. Their capability for sustained and stimuli-responsive release helps minimize systemic side effects while enhancing treatment effectiveness. Moreover, their adaptability for combination therapies and ability to mimic natural biological environments make them a powerful and innovative platform in advanced drug delivery, particularly in cancer care.
Table 1: summary on nanofibers in drug delivery system
|
Category |
Key-point |
Details |
||
|
Tumour Modelling |
Biomimetic systems |
Mimic tumour microenvironment, enabling improved drug screening and testing [7]. |
||
|
Drug Delivery |
|
Allow targeted delivery with prolonged release, reducing systemic toxicity and improving bioavailability [8]. |
||
|
Structural Features |
Material advantages |
High surface area, porosity, tunable morphology, and strong mechanical properties [9] |
||
|
Diagnostics |
Cancer detection |
Enable capture of circulating tumour cells and sensitive biomarker detection [10]. |
||
|
Biosensing |
Early detection |
Surface supports biomolecule immobilization for high-sensitivity diagnostics [10]. |
||
|
Smart Systems |
Stimuli-responsive release |
Respond to pH, temperature, light, and magnetic fields for controlled drug release [11]. |
||
|
Advanced Design |
Core–sheath nanofibers |
|
2. FABRICATION TECHNOLOGIES
2.1 Electrospinning for Oncological Drug Delivery
Electrospinning is the most widely investigated nanofiber fabrication technique in oncology. In the 21st century, chemotherapy stands as a primary treatment method for prevalent diseases, yet drug resistance remains a pressing challenge. Utilizing electrospinning to support chemotherapy drugs offers sustained and controlled release methods in contrast to oral and implantable drug delivery modes, which enable localized treatment of distinct tumor types [13].
Among various techniques available for nanofiber fabrication, electrospinning produces nanofibers with high interconnected pores in the nanoscale range, having also a large surface area-to-volume ratio, high inter-fiber porosity, low hindrance for mass transfer, flexible handling, adjustable morphology, and high mechanical strength, which make nanofibers useful as therapeutic patches or mats for biomedical applications [9].
Recent advances in electrospun nanofibers in cancer research include the incorporation of drugs, control of release kinetics, orientation and alignment of nanofibers, and the fabrication of 3D nanofiber scaffolds, with applications spanning local chemotherapy, combinatorial therapy, cancer detection, cancer cell capture, regulation of cancer cell behavior, construction of in vitro 3D cancer models, and engineering of bone microenvironments for cancer metastasis [14].
2.1.1. Coaxial Electrospinning for Targeted Cancer Therapy
A major advancement over conventional electrospinning is the coaxial configuration, which produces core-sheath nanofiber architectures. Coaxial electrospinning offers several potential advantages for cancer treatment, including an enhanced drug loading capacity, the improved stability and bioavailability of therapeutic agents, and the ability to tailor the properties of the nanofibers for specific applications [10].
The core–sheath structure in electrospinning bears advantages in dual-drug loading: the core and sheath layers can carry different drugs, facilitating collaborative treatment to counter chemotherapy drug resistance. This approach minimizes patient discomfort associated with multiple-drug administration [13].
In breast cancer specifically, electrospun fibers serve as vehicles for chemotherapy drug delivery localized to the site, enabling dosage adjustment based on patch thickness and total area. Coaxial electrospinning has been used to load doxorubicin (DOX), an anticancer drug, onto nanofibers — resulting in a mortality rate of approximately 57% for MCF-7 breast cancer cells after 7 days. Another development introduced an implantable hierarchical microfiber device using coaxial electrospinning, forming periodically arranged chambers within a fiber matrix, with doxorubicin hydrochloride within these chambers exhibiting rapid release, effectively eliminating the remaining tumor cells and curbing tumor recurrence [13].
For cervical cancer, coaxial electrospinning has been used to fabricate micro/nanofibers with sheath/core structures of different polymers in a single step, thereby achieving improved combined properties. These systems offer significant advantages, such as high loading capacity due to the large surface area, prolonged and controlled drug release, flexibility, biodegradability and biocompatibility [15].
2.1.2. Stimuli-Responsive Electrospun Nanofibers in Cancer Treatment
One of the most promising oncological innovations is stimuli-responsive nanofiber systems. Stimuli-responsive nanofibers prepared by electrospinning can respond extremely quickly to external environmental stimuli. As an intelligent drug delivery platform, stimuli-responsive nanofibers can efficiently load drugs and then be stimulated by specific conditions light, temperature, magnetic field, ultrasound, pH or reactive oxygen species (ROS) to achieve slow, on-demand, or targeted release, showing great potential in areas such as drug delivery and tumor therapy [16].
The use of stimuli-responsive polymers enables on-demand release of encapsulated drugs because the polymer can sense and respond to signals and variations in the surrounding environment, leading to microstructure change and drug release [14]. For example, magnetic nanoparticles (MNPs) and anticancer drug DOX were encapsulated into nanofibers composed of a temperature-responsive copolymer, leading to 70% death of human melanoma cells with exposure to 5 minutes of alternating magnetic field due to a synergistic effect of chemotherapy and hyperthermia [14].
The restorative viability of anticancer medicinal nanofiber systems is expanded by planned multi-drug/nanofiber preparation, the preparation of nanofibers from polymers that can sense both temperature and pH, and the fabrication of magnetic nanomaterials for the utilization of drug delivery and hyperthermia treatment [10].
2.2. Magnetic Nanofibers and Hyperthermia Therapy
Magnetic hyperthermia is a field that originated from the use of magnetic nanomaterials, which, due to their magnetic properties and other characteristics, are used in many clinical trials as one of the solutions for cancer treatment. Magnetic nanomaterials can increase the temperature of nanoparticles located in tumor tissue by applying an alternating magnetic field. A very simple, inexpensive, and environmentally friendly method is the fabrication of various types of functional nanostructures by adding magnetic additives to the spinning solution in the electrospinning process, which can overcome the limitations of this challenging treatment process [17].
Studies have shown that electrospun poly(caprolactone)/Fe?O? magnetic nanofibers, when subjected to an alternating magnetic field, can generate heat reaching approximately 45 °C, which can then be transferred to cancerous tissue and cause cancer cells to die [17].
Hyperthermia induces endoplasmic reticulum-mediated apoptosis in melanoma and non-melanoma skin cancer (NMSC) cells. Further, hyperthermia can reverse the chemo drug resistance of cells and enhance drug activity. Low doses of hyperthermia can enhance anticancer drug efficacy by modifying responsible gene expression, for example, reducing the MDR1 gene expression, which increases drug sensitivity. Therefore, the combination of hyperthermia and drug delivery can enhance the efficacy of treatment by reducing cellular resistance toward anticancer drugs [18].
2.3. Force Spinning for Light-Responsive Cancer Drug Delivery
Unlike electrospinning, force spinning generates fibers by centrifugal forces rather than electrostatic forces, resulting in significantly higher fiber production. The functionalization of nanocarriers on nanofibers can result in smart nanofibers with anticancer capabilities that can be activated by external stimuli, such as light. This approach has been explored for dual-stimuli-responsive systems that offer high-precision tumor targeting through nano-in-nanofiber emerging delivery systems for dual-controlled drug release [19].
2.4. Post-Surgical and Implantable Nanofiber Systems
A critical oncological application of fabricated nanofibers is the prevention of local tumor recurrence after surgical resection. Post-surgical chemotherapy in pancreatic cancer has notorious side effects due to the high dose required. Controlled and sustained local delivery of a reduced drug dose from an irinotecan-loaded electrospun nanofiber membrane placed on the patient's tissue after tumor resection surgery has been demonstrated using polycaprolactone (PCL), with mechanical properties and release kinetics adjusted by electrospinning parameters [20].
Nanofiber mats with a high surface area and controllable pores can potentially diagnose and treat cancer cells. Nanofibers, with the addition of anticancer drugs, can give sustained release after cancer tumor removal; however, there is a need to produce more advanced materials which will support the complicated treatment after tumor removal [21].
2.5. Polymeric Materials Used in Oncological Nanofibers
A number of polymers like cellulose, chitosan, Polyvinyl Alcohol (PVA), Polyacrylonitrile (PAN), peptides, and Poly(hydroxy alkanoate) have good properties for the treatment of cancer, but nanofiber-based targeted and controlled drug delivery systems produced by co-axial electrospinning have extraordinary properties like favorable mechanical characteristics, an excellent release profile, a high surface area, and high sponginess, and are harmless, bio-renewable, biofriendly, highly degradable, and can be produced very conveniently on an industrial scale [10].
Biopolymer nanofiber membranes, distinguished by their high surface area-to-volume ratio, biocompatibility, and biodegradability, are ideally suited for pharmaceutical and biomedical applications [22].
3. THERAPEUTIC STRATEGIES
Table 2: Nanofiber based therapeutic strategies for oncological applications
|
Chemotherapy [23] |
Induction of apoptosis or mitosis arrest via DNA damage or inhibition of cell division |
Localized, sustained release of chemotherapeutics (eg: doxorubicin, paclitaxel) directly at the tumor resection site; codelivery of multiple drugs from coaxial fibers |
Reduces systemic toxicity. Overcomes multidrug resistance via local concentration. Prevents tumor recurrence post-surgery. |
Breast, glioblastoma, ovarian, colorectal |
|
Photothermal Therapy [24] |
Converts near-infrared light into localized heat (>50°C) to denature and ablate cancer cells |
Incorporation of photothermal agents (graphene oxide, gold nanorods, polydopamine) into fiber matrix; flexible mats conform to irregular tumor surfaces |
Minimally invasive, precise spatial control, and synergistic potential with chemotherapy from the same fiber |
Melanoma, breast, |
|
Photodynamic therapy [25] |
Generates reactive oxygen species (primarily singlet oxygen) upon light activation of a photosensitizer |
Prevents photosensitizer aggregation; enhanced oxygen permeability improves ROS production; enables sustained release for repeated sessions |
Avoids systemic photosensitivity, higher quantum yield of ROS, and wavelength-specific activation for superficial or deep tumors |
Skin, esophageal, bladder |
|
Immunotherapy [26] |
Stimulates or modulates the host immune system via checkpoint inhibition, cytokine activation, or vaccine priming |
Mimics extracellular matrix to recruit immune cells; serves as scaffold for localized delivery of checkpoint inhibitors (anti-PD-1) or STING agonists |
Reduces immune-related adverse events, enables in situ vaccination, and provides sustained immune activation |
Melanoma, glioma, lymphoma |
|
Gene therapy [27] |
Introduces nucleic acids (siRNA, miRNA, pDNA, CRISPR-Cas9) to silence oncogenes or edit DNA |
Protects vulnerable nucleic acids from enzymatic degradation; enables sustained, localized transfection; allows codelivery with cationic polymers |
Overcomes poor cellular uptake and rapid clearance, reduces off-target editing risks, and enables long-term gene silencing with single application |
Pancreatic, liver, lung |
4. CHALLENGES IN CLINICAL TRANSLATION
i. Biological Complexity and Tumor Heterogeneity
One of the primary barriers to clinical translation is the highly heterogeneous tumor microenvironment, which significantly influences nanocarrier distribution, penetration, and therapeutic response. Variability in vascularization, stromal density, and immune cell infiltration leads to inconsistent drug accumulation and efficacy across patients [28][29].
Additionally, the widely exploited enhanced permeability and retention (EPR) effect is often unreliable in humans, despite promising preclinical outcomes, thereby limiting effective tumor targeting [30].
ii. Poor Predictability from Preclinical Models
Nanofiber-based systems frequently show strong efficacy in in vitro and animal models, but fail in clinical settings due to poor translational predictability. Differences in physiology between animal models and humans especially in nanoparticle biodistribution and clearance lead to discrepancies in therapeutic outcomes [28].
Moreover, the lack of reliable biomarkers and patient stratification tools further complicates translation, resulting in suboptimal clinical trial outcomes [29].
iii. Safety, Toxicity, and Immunogenicity Concerns [28]
Nanofiber-based delivery systems may introduce unexpected toxicity profiles due to altered pharmacokinetics and biodistribution. Accumulation in off-target organs (e.g., liver, spleen, lymph nodes) and long-term persistence raise safety concerns.
Furthermore, immune reactions, including complement activation and hypersensitivity, are difficult to predict during preclinical evaluation and may lead to clinical failure.
iv. Complexity of Design and Characterization [31]
Nanofiber systems often involve multicomponent architectures (polymer matrix, drug, targeting ligands, nanoparticles), making their physicochemical characterization challenging. Critical attributes such as fiber diameter, drug loading, release kinetics, and surface properties must be tightly controlled, as they directly influence biological performance.
This complexity also contributes to batch-to-batch variability, affecting reproducibility and regulatory approval.
v. Manufacturing and Scale-Up Limitations [31]
Scaling up nanofiber fabrication techniques (e.g., electrospinning) from laboratory to industrial level remains a major hurdle. Challenges include:
These issues lead to high production costs and limited commercial feasibility, hindering widespread clinical adoption.
vi. Regulatory and Standardization Challenges
The absence of harmonized regulatory guidelines for nanomedicines complicates approval pathways. Regulatory agencies require extensive data on safety, efficacy, and quality, but standardized protocols for nanofiber systems are still evolving [31].
Additionally, uncertainty in classification (drug vs device vs combination product) delays regulatory decisions.
vii. Clinical Trial Design and Translational Gaps
Clinical translation is further hindered by poorly designed clinical trials, including:
These factors contribute to low success rates in late-stage clinical trials, despite promising preclinical data [29].
viii. Economic and Commercial Barriers
Nanofiber-based oncological systems are often expensive to develop and produce, raising concerns about cost-effectiveness compared to conventional therapies.
For successful translation, a formulation must demonstrate clear clinical superiority (efficacy or safety) to justify higher costs otherwise adoption by healthcare systems remains unlikely [28].
5. FUTURE PERSPECTIVES AND CONCLUSION
Nanofiber-based oncological platforms are rapidly evolving beyond single-drug, single-stimulus constructs toward highly integrated, multi-modal smart systems. The integration of patient-specific multi-omics data with artificial intelligence is converting tumour heterogeneity into quantitative design rules for nanocarrier optimisation, with AI-guided digital twins coupled with adaptive delivery enabling real-time, personalised dosing transforming nanomedicine from an empirical carrier technology into a patient-calibrated, closed-loop therapeutic engine [32]. Applied to nanofibers, machine learning algorithms can predict fiber diameter, drug loading efficiency, and release kinetics as functions of fabrication parameters, substantially reducing optimisation timelines and enabling rational, tumour-specific scaffold design.
The next generation of nanofiber platforms will increasingly harness stimuli-responsive, multi-modal architectures combining pH-responsive chemotherapy release, photothermal agents, photosensitisers, and immunomodulatory or gene-silencing payloads within a single coaxial or triaxial construct to simultaneously target multiple hallmarks of cancer and overcome adaptive therapeutic resistance. Integration with tumour-on-chip and organ-on-chip microfluidic systems will provide biomimetic preclinical screening environments that more faithfully recapitulate the hypoxic, acidic tumour microenvironment, improving the predictive validity of in vitro studies and narrowing the translational gap.
Achieving clinical translation, however, necessitates resolving the persistent barriers of manufacturing scalability, regulatory harmonisation, and long-term in vivo safety characterisation. Despite over 15 FDA-approved cancer nanomedicines and a robust clinical pipeline, translation is impeded by biological barriers, manufacturing scalability issues, and a fragmented regulatory landscape challenges requiring safe-by-design engineering and quality-by-design modular manufacturing as convergent translational strategies [12]. Current regulatory frameworks evaluate polymer-based nanotherapeutics under conventional pharmaceutical and biological regulations, overlooking nanospecific properties and leading to case-by-case assessments; key issues include inadequate characterisation of physicochemical properties and limited predictability of in vivo performance, underscoring the need for a harmonised, science-driven regulatory framework [13]. Finally, as the global cancer burden falls disproportionately on low- and middle-income countries, equity and accessibility must be embedded as design and policy principles with cost-effective manufacturing models and context-sensitive clinical trial designs developed in parallel with scientific advances.
In conclusion, nanofiber-based oncological platforms stand at a critical inflection point transitioning from compelling proof-of-concept to the threshold of clinical validation. The convergence of advanced fabrication science, precision oncology, tumour microenvironment biology, AI-assisted design, and increasingly robust regulatory frameworks positions nanofiber technology as a credible and indispensable component of the next generation of cancer therapeutics. Realising its full translational potential will demand sustained interdisciplinary collaboration among materials scientists, oncologists, pharmacologists, regulatory scientists, and health policy-makers united by the shared imperative of translating nanoscale innovation into meaningful improvements in cancer outcomes for patients worldwide.
REFERENCES
Nancy Varghese, Prasanth M S, Anakha S Kuttan, Nanofiber Based Platforms for Oncological Applications: Fabrication, Therapeutic Strategies and Translational Properties Int. J. of Pharm. Sci., 2026, Vol 4, Issue 5, 5313-5323, https://doi.org/10.5281/zenodo.20310482
10.5281/zenodo.20310482