Smart Tumor Microenvironment-Responsive Nanotheranostic Agent for Effective Cancer Therapy

The tumor microenvironment (TME), which includes acidic and hypoxic conditions, severely impedes the therapeutic efficacy of antitumor agents. Herein, MnO2-loaded, bovine serum albumin, and PEG co-modified mesoporous CaSiO3 nanoparticles (CaM-PB NPs) are developed as a nanoplatform with sequential theranostic functions for the engineering of TME. The MnO2 NPs generate O-2 in situ by reacting with endogenous H2O2, relieving the hypoxic state of the TME that further modulates the cancer cell cycle status to S phase, which improves the potency of co-loaded S phase-sensitive chemotherapeutic drugs. After the hypoxia relief, CaM-PB can sustainably release drugs due to the enlarged pores of mesoporous CaSiO3 in the acidic TME, preventing the drug pre-leakage into the blood circulation and insufficient drug accumulation at tumor sites. Moreover, the Mn2+ released from the MnO2 NPs at tumor sites can potentially serve as a diagnostic agent, enabling the identification of tumor regions by T-1-weighted magnetic resonance imaging during therapy. In vivo pharmacodynamics results demonstrate that these synergetic effects caused by CaM-PB NPs significantly contribute to the inhibition of tumor progression. Therefore, the CaM-PB NPs with sequential theranostic functions are a promising system for effective cancer therapy.