Artemisinin co-delivery system based on manganese oxide for precise diagnosis and treatment of breast cancer.

Tumor microenvironment (TME) responsive intelligent system can realize the specific release and uniform distribution of chemotherapy drugs in tumor tissues, to achieve high-efficiency and low-toxic treatment of tumors. In this paper, drug delivery system TKD@RBCm-Mn2O3-ART with the above characteristics was constructed. We synthesized hollow mesoporous manganese trioxide (Mn2O3) nanoparticles and firstly found that they owned time-dependent size transformation feature in simulated TME. The particle size decreased from 318nm to 50nm and 6nm at 1h and 4h in simulated TME, respectively. Then artemisinin (ART) was loaded into Mn2O3 to realize the co-delivery of Mn2+ and ART. The modification of homologous red cell membrane (RBCm) and TKD peptide was aimed at long circulation and tumor targeting in the body. In vitro results demonstrated that in the presence of GSH, the cumulative drug release percentage could achieve 97.5%. Meanwhile, Mn2O3 exhibited a good imaging capability in tumor, with the relaxation rate of 6.3113 mM-1S-1. After entering into MCF-7 cells, TKD@RBCm-Mn2O3/ART quickly released Mn2+ and ART synchronously to generate large amount of ROS, inducing DNA damage. In vivo results proved TKD@RBCm-Mn2O3/ART could deliver drug to the deep area of solid tumors, and achieve accurate diagnosis and treatment of breast cancer.