Nanofiber-Based Drug Delivery and Extracellular Matrix-Mimetic Platforms in Cancer Therapy: From Engineering Design to Clinical Translation.

The nanofiber-based drug delivery systems offer a high surface-area-to-volume ratio, tunable porosity, controllable degradation, and superior drug-loading capacity, making them promising platforms for precision cancer therapy. This review details the engineering design, fabrication methods and biomedical uses of nanofibers for cancer therapeutics, as well as for extracellular matrix (ECM)-mimicking tumor models. The major fabrication techniques such as electrospinning, phase separation, self-assembly, and template synthesis are critically examined, and their impact on the fiber morphology, drug packaging, and drug release are highlighted. Electrospun nanofibers closely replicate the native ECM architecture, which allows for the creation of physiologically relevant 3-D tumor models for the study of tumor progression, metastasis, and therapeutic resistance. Recent studies have shown that nanofibrous platforms can be used to deliver chemotherapeutics, genes, and combination therapies locally and in a stimulus-responsive manner, leading to increased cytotoxicity, extended release times, and decreased systemic toxicity in models of breast cancer, melanoma, pancreatic cancer, and colorectal cancer. The applications of nanofibers in precision oncology are further highlighted by advanced multifunctional systems based on magnetic nanoparticles, pH-responsive carriers, and core-shell architectures. Commercial products, patents, and current clinical trials further highlight the increasing translational importance of nanofiber technologies. However, issues in large-scale manufacturing, residual solvent toxicity, reproducibility, long-term biocompatibility and regulatory standardization remain to be clinically translated. The use of artificial intelligence, computational models and automated manufacturing could further drive the emergence of clinically translatable and scalable nanofiber-based cancer therapeutics.