MnO 2 Gatekeeper: An Intelligent and O 2 ‐Evolving Shell for Preventing Premature Release of High Cargo Payload Core, Overcoming Tumor Hypoxia, and Acidic H 2 O 2 ‐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.