Dextran-based prodrug-nanoassemblies responsively releasing pidotimod and camptothecin for anti-breast cancer.

Objective: The aim of this study was to develop a pH/GSH-responsive dextran-based drug delivery system, co-delivering camptothecin (CPT) and pidotimod (PTD), to increase anti-breast cancer efficacy.

Methods: CPT was grafted onto dextran via disulfide bond, and PTD were concurrently conjugated into dextran by the instrumentality of ester bond. The synthesized conjugate could self-assemble to form prodrug-nanoassemblies (CPT-SS-DEX-PTD NPs) in solution. The feature of prodrug-nanoassemblies was assayed, and the synergetic effect of chemo-immunotherapy against solid tumor was investigated in 4T1 breast cancer xenograft models.

Results: The CPT-SS-DEX-PTD NPs were approximately spherical and about 180 nm. In drug release experiment, the prodrug-nanoassemblies showed more prolonged circulation time and selective pH or GSH-responsive release profile. The PTD was released in weak acidity tumor microenvironment (TME), then induced immune cells to activate and secret anti-tumor cytokines. The CPT was released via GSH-responsive in tumor cell to exert anti-tumor efficiency. In 4T1 breast cancer model, the CPT-SS-DEX-PTD NPs displayed synergistic anti-tumor efficacy and lower side effects of CPT due to the combination of chemo-immunotherapy.

Conclusions: The dextran-based pH/GSH-responsive prodrug-nanoassemblies with synergistic therapy efficacy and low systemic toxicity may offer a novel strategy for breast cancer therapy.