MnO2 Gatekeeper: An Intelligent and O2‐Evolving Shell for Preventing Premature Release of High Cargo Payload Core, Overcoming Tumor Hypoxia, and Acidic H2O2‐Sensitive MRI

Premature leakage of photosensitizer (PS) from nanocarriers significantly reduces the accumulation of PS within a tumor, thereby enhancing nonspecific accumulation in normal tissues, which inevitably leads to a limited efficacy for photodynamic therapy (PDT) and the enhanced systematic phototoxicity. Moreover, local hypoxia of the tumor tissue also seriously hinders the PDT. To overcome these limitations, an acidic H 2 O 2 ‐responsive and O 2 ‐evolving core–shell PDT nanoplatform is developed by using MnO 2 shell as a switchable shield to prevent the premature release of loaded PS in core and elevate the O 2 concentration within tumor tissue. The inner core SiO 2 ‐methylene blue obtained by co‐condensation has a high PS payload and the outer MnO 2 shell shields PS from leaking into blood after intravenous injection until reaching tumor tissue. Moreover, the shell MnO 2 simultaneously endows the theranostic nanocomposite with redox activity toward H 2 O 2 in the acidic microenvironment of tumor tissue to generate O 2 and thus overcomes the hypoxia of cancer cells. More importantly, the Mn(ΙΙ) ion reduced from Mn(ΙV) is capable of in vivo magnetic resonance imaging selectively in response to overexpressed acidic H 2 O 2 . The facile incorporation of the switchable MnO 2 shell into one multifunctional diagnostic and therapeutic nanoplatform has great potential for future clinical application.