Gelatin nanocarriers in oncology: A biocompatible strategy for targeted drug delivery

Cancer persists as a formidable global health crisis, with conventional therapies often compromised by systemic toxicity, poor tumor specificity, and therapeutic resistance. Nanotechnology has emerged as a transformative approach, leveraging nanoscale materials to enhance drug bioavailability, enable targeted delivery, and mitigate off-target effects. Among these innovations, gelatin-based nanoparticles (GNPs), derived from collagen and endorsed by the FDA have garnered significant attention as biocompatible, biodegradable nanocarriers uniquely suited for oncology applications. GNPs address critical extracellular barriers such as inefficient tumor penetration, rapid clearance, and nonspecific biodistribution by capitalizing on gelatin's intrinsic advantages: low immunogenicity, tumor microenvironment responsiveness (pH, enzymes, redox gradients), and tunable surface functionalization. This review highlights the versatility of GNPs in overcoming these challenges through advanced strategies like ligand-mediated targeting, combinatorial therapies, and size-transformable systems that enhance tumor accumulation and therapeutic precision. Case studies across lung, breast, skin, liver, colorectal, brain, and head/neck cancers demonstrate GNPs' ability to reduce IC50 values by 2 to 4-fold, achieve >90 % apoptosis in malignant cells, and minimize damage to healthy tissues. Despite the challenges in translating gelatin-based nanocarriers from preclinical studies to clinical applications in cancer therapy, their promising preclinical performance highlights their potential as patient-centric platforms capable of advancing precision oncology. Further their adaptability, multifunctionality, and capacity for stimuli-responsive drug release underscore their potential to improve clinical outcomes, offering a targeted, low-toxicity paradigm for managing diverse malignancies.