Cell membrane camouflaged Cu-doped mesoporous polydopamine for combined CT/PTT/CDT synergistic treatment of breast cancer

Currently, traditional monotherapy for cancer often results in indiscriminate attacks on the body, leading to the emergence of new health problems. To confront these challenges, multimodal combination therapy has become necessary. However, how to develop new smart nanomaterials through green synthesis methods, delivering drugs while simultaneously synergizing multimodal combination therapies for tumor treatment, remains a topic of great significance. In this study, a biomimetic composite nanomaterial (RM-Cu/P) composed of mesoporous polydopamine (MPDA) as the core and red blood cell membranes (RBCMs) as the shell was synthesized as a drug carrier to deliver doxorubicin (DOX) while achieving synergistic chemotherapy, photothermal and chemodynamic therapy (CT/PTT/CDT). Herein, the nanoparticles were extensively characterized to examine their morphological characteristics, elemental composition, and drug-carrying capacity. Notably, the coating of RBCM reduced the toxicity of the RM-Cu/P@DOX nanoparticles, improved their targeting ability and prolonged their circulation time in vivo. The Cu-doped nanoparticles were capable of initiating a Fenton-like reaction to generate reactive oxygen species (ROS) for CDT, while the photothermal conversion efficiency (η) reached 45.20 % under NIR laser irradiation. Subsequently, the particles were examined by in vivo and in vitro experimental studies in cytotoxicity, cellular uptake, ROS levels, lysosomal escape, and mouse tumor model to evaluate their potential application in antitumor. Compared with monotherapy, the RM-Cu/P@DOX nanoparticles had multiple-stimulation response properties under redox, pH, and NIR, which exhibited the advantage of combined trimodal therapy, resulting in remarkable synergistic antitumor efficacy. In conclusion, this innovative platform exhibited promising applications in smart drug delivery and synergistic treatment of cancer.