Stabilization of chitosan-based nanomedicines in cancer therapy: a review

Chitosan (CS), a versatile and alkaline polysaccharide, has gained significant attention in nanomedicine due to its biocompatibility and biodegradability. In recent years, its applications in cancer therapy, particularly for the delivery of chemotherapeutic drugs, diagnostic agents, and genes, have advanced considerably. However, many CS-based nanomedicines suffer from poor stability in biological fluids, especially under physiological conditions. The neutral pH and the presence of electrolytes in physiological environments reduce the charge density of CS, which can account for this application limitation of CS-based nanomedicines. To improve the stability and prevent dissociation or aggregation of these nanomedicines before reaching the target sites, this review summarizes common stabilization strategies including hydrophilic or hydrophobic modification of CS, as well as incorporation with metal ions (e.g. Fe³⁺ or Zn²⁺), complexation with anionic cross-linkers (e.g. TPP) or anionic polymers. Additionally, the review highlights the application of stabilized CS-based nanocarriers in drug delivery, with a particular focus on cancer therapy. The challenges and future perspectives for accelerating the clinical translation of these nanomedicines are also discussed.