Core-shell nanomaterials engineered to reverse cancer multidrug resistance by immunotherapy and promote photo-responsive chemotherapy

Cancer immunotherapy has already become a critical hallmark in clinical cancer therapy, especially through tumor associated macrophages (TAMs) polarization. Because multidrug resistance (MDR) hinders the efficiency of chemotherapy, immunotherapy was also incorporated in regulation of MDR. Herein, Au nanocages encapsulated with doxorubicin (Dox) by the phase change material were fabricated with a layer consisting of calcium and ferrous carbonates (FeCaC), and achieved Au-DP@FeCaC NPs could reprogram TAMs from immunosuppressive M2 to immunostimulatory M1 based on the intrinsic property of FeCaC shell. Nitric oxide (NO) could be produced by M1 TAMs to inhibit P-glycopmtein (P-gp) expression. Then, FeCaC shell of Au-DP@FeCaC NPs could be degraded at the acidic condition and NIP laser irradiation would further facilitate to thermally release Dox. A series of in vitro and in vivo assessments confirmed Au-DP@FeCaC NPs could realize the immunotherapy-mediated highly efficient chemotherapy of MDR cancer.

Automated summary

This study successfully reprogrammed tumor-associated macrophages (TAMs) from immunosuppressive to immunostimulatory state using Au-DP@FeCaC NPs, and achieved efficient chemotherapy of multidrug-resistant (MDR) cancer by releasing doxorubicin (Dox) under acidic conditions.