Studies on the anti-tumor effects of curcumin synergizing with doxorubicin in inducing immunogenic cell death.

Chemotherapy-induced immunogenic cell death (ICD) remodels the immunosuppressive tumor microenvironment and enhances chemotherapeutic efficacy. In this study, a nanoparticle delivery system, designated as CMCS-D + C/NPs, is constructed using polyethylene glycol-poly (β-amino ester) as the carrier to encapsulate doxorubicin (DOX) and curcumin (Cur), with carboxymethyl chitosan (CMCS) coated on the surface. The CMCS-D + C/NPs exhibit pH-responsive properties, enabling targeted accumulation at tumor sites and controlled drug release. DOX induces ICD by promoting reactive oxygen species generation and triggering endoplasmic reticulum (ER) stress, whereas Cur also elicits ER stress, thereby compensating for the insufficient immunogenicity of DOX. The CMCS-D + C/NPs demonstrate enhanced cellular uptake and apoptosis-inducing capabilities. Moreover, they effectively promote CRT exposure, HMGB1 release, and ATP secretion in 4T1 cells. Furthermore, in a murine breast cancer model, CMCS-D + C/NPs significantly upregulate the expression of proteins such as CD8 and Caspase-3, cytokines (IFN-γ and IL-6), and Granzyme B, demonstrating favorable antitumor efficacy.