(A) Activation mechanism of MCC nanosystems for highly efficient phototherapy and acute immune response. The MCC nanosystems can be prepared by self-assembly of CyI and chitosan, after which the MnO2 nanoparticles are formed as a shell by electrostatic interaction and Mn-N coordinate bonding. After intravenous injection, MCC nanosystems can efficiently deliver photosensitizers into tumor cells. Once endocytosed, MCC could be responsive to TME and dual-modulate tumor hypoxia to enhance NIR-guided phototherapy and acute immune response simultaneously in order to combat primary and metastatic tumors; (B) Photos of CyI, CC, and MCC in water solution under ambient light and NIR light; (C) The XPS spectrum analysis of Mn [IV] 2p peak from MCC; Absorption (D) and fluorescence (E) spectra of CyI, CC, and MCC, with the concentrations of CyI in DMSO, CC, and MCC are 25 µM, 25 µM, and 15 µM, respectively; (F) TEM images of CC and MCC in the presence or absence of 10 mM GSH or 50 µM H2O2 solution, respectively (bar, 500 nm); Inset photos are enlarged TEM images of CC and MCC (bar in CC, 10 nm; bar in MCC, 50 nm).