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

[Display omitted] •• Au NCs could thermally convert PCM and release Dox under NIR laser irradiation.•• FeCaC coating layer on Au NCs could reprogram TAMs from M2 to M1 phenotype.•• NO produced from M1 TAMs could inhibit the P-gp expression and enhance chemotherapy.•• Efficient immunotherapy-mediated chemotherapy was realized. 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 DPAu@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-glycoprotein (P-gp) expression. Then, FeCaC shell of DPAu@FeCaC NPs could be degraded at the acidic condition and NIR laser irradiation would further facilitate to thermally release Dox. A series of in vitro and in vivo assessments confirmed DPAu@FeCaC NPs could realize the immunotherapy-mediated highly efficient chemotherapy of MDR cancer.