Gossypol-based nanocarriers for cancer treatment: advances and future perspectives

Gossypol, a polyphenolic aldehyde derived from cotton plants, has emerged as a potent natural anticancer agent due to its ability to modulate multiple cellular pathways, including apoptosis, angiogenesis, and cell cycle arrest. Despite its promising therapeutic potential, the clinical application of gossypol has been limited by poor aqueous solubility, rapid metabolism, systemic toxicity, and low bioavailability. Nanocarrier-based drug delivery systems offer an innovative strategy to overcome these challenges, enabling targeted delivery, enhanced stability, and reduced off-target effects. This review comprehensively discusses the pharmacological profile of gossypol, its mechanisms of anticancer action, and the limitations associated with its conventional use. The review explores a diverse array of nanocarrier platforms such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, dendrimers, micelles, and hybrid systems that have been engineered to improve gossypol's therapeutic index in both in vitro and in vivo models. Furthermore, the review addresses the formulation challenges, toxicity concerns, and regulatory barriers associated with nanocarrier development. Finally, the review highlights emerging trends, including exosome-mediated delivery and biomimetic systems, and discusses the future of personalized nanomedicine and translational pathways for clinical adoption. Gossypol-loaded nanocarriers represent a promising frontier in cancer therapy, potentially bridging the gap between natural product efficacy and clinical applicability.