The tumor microenvironment (TME), which includes acidic and hypoxic conditions, severely impedes the therapeutic efficacy of antitumor agents. Herein, MnO 2 -loaded, bovine serum albumin, and PEG co-modified mesoporous CaSiO 3 nanoparticles (CaM-PB NPs) are developed as a nanoplatform with sequential theranostic functions for the engineering of TME. The MnO 2 NPs generate O 2 in situ by reacting with endogenous H 2 O 2 , 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 CaSiO 3 in the acidic TME, preventing the drug pre-leakage into the blood circulation and insufficient drug accumulation at tumor sites. Moreover, the Mn 2+ released from the MnO 2 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.
Keywordshypoxia relief, mesoporous calcium silicate, sequential functions, sustained drug release, synergetic effects