Exosome-camouflaged chitosan/zinc oxide/carbon quantum dot nanocarriers for pH-responsive doxorubicin delivery in breast cancer treatment.

Doxorubicin (DOX) chemotherapy for breast cancer is constrained by systemic toxicity and limited tumor selectivity, underscoring the need for polysaccharide-based carriers in which pH responsiveness arises from intrinsic polymer properties rather than chemical modification. In this study, a carbohydrate-centered biomimetic nanocarrier was developed using chitosan as the primary structural and pH-responsive matrix, integrating zinc oxide nanoparticles (ZnO) and carbon quantum dots (CQDs) through a W1/O/W2 double-emulsion process, followed by surface association with bone marrow-derived mesenchymal stem cell (BM-MSC) exosomal membranes. The resulting CS/ZnO/CQDs@DOX nanocarriers exhibited an average hydrodynamic diameter of ∼180 nm, which increased to ∼205 nm after exosome association, accompanied by partial surface charge shielding. Physicochemical analyses supported a predominantly non-covalent assembly without evidence of alteration of the chitosan backbone, yielding a high encapsulation efficiency (88.75 ± 2.1%) and a drug loading of 6.8 ± 0.5 wt%. In vitro studies revealed pronounced pH-dependent doxorubicin release and enhanced cytotoxicity toward MCF-7 cells IC₅₀ = 0.8 ± 0.1 μM, while maintaining minimal toxicity toward normal cells. Overall, these findings demonstrate that chitosan-driven pH responsiveness, complemented by inorganic components and biomimetic surface camouflaging, provides an effective and chemically conservative strategy for carbohydrate-based drug delivery design.