Multifunctional chitosan–doxorubicin nanocarriers: advancing targeted breast cancer chemotherapy

Breast cancer remains one of the leading causes of cancer-related mortality worldwide, with chemotherapy continuing to play a central role in clinical management. Doxorubicin, despite its potent antitumor activity, suffers from severe dose-limiting cardiotoxicity, poor tumor selectivity and the rapid emergence of multidrug resistance. Chitosan, a naturally derived biocompatible polysaccharide, has emerged as a versatile nanocarrier platform capable of addressing these limitations through intelligent design strategies. This review explores how chitosan-based doxorubicin nanoplatforms have been engineered to recognize cancer cell surface markers, respond to tumor-specific cues such as acidic pH and elevated glutathione, and deliver drug combinations that dismantle resistance mechanisms. We examine both systemic nanoparticulate systems and innovative localized depots including injectable gels, implantable matrices and even oral bacteria-assisted carriers that concentrate chemotherapy at the tumor site while sparing healthy tissues. By detailing the intracellular journey of these nanoplatforms from receptor binding to nuclear DNA damage and apoptosis induction, this review illuminates the molecular basis of their enhanced efficacy. Finally, we discuss the translational challenges and future directions needed to bring these promising chitosan nanomedicines from bench to bedside for improved breast cancer outcomes.