Tumor‐Activated Photosensitization and Size Transformation of Nanodrugs

Abstract Effective intratumoral distribution of anticancer agents with good tumor penetration is of practical importance for photo‐chemotherapy. Herein, a metal‐organic framework (MOF) assisted strategy is reported for smart delivery of aggregation‐induced emission photosensitizer (AIE PS) and chemodrug for deep tumor penetration to realize effective image‐guided photo‐chemotherapy. A newly designed AIE PS is loaded inside an iron(III) carboxylate‐based MOF, MIL‐100, to produce PS@MIL‐100, which is encapsulated by doxorubicin (Dox) conjugated poly(ethylene glycol) methyl ether (PEG) to yield Dox‐PEG‐PS@MIL nanoparticles (NPs) with a diameter of 120 nm. After Dox‐PEG‐PS@MIL NPs reached the tumor site, intratumoral H 2 O 2 can cause the release of the loaded PS at the tumor surface for activatable photodynamic therapy (PDT). The Dox‐PEG segment is simultaneously triggered to self‐assemble into ultrasmall Dox NPs. Under light irradiation, PDT is activated at the tumor surface, synergistically enhancing the tumor penetration of Dox NPs along with their ultrasmall size. After endocytosis of Dox NPs, free Dox is released from Dox NPs under low pH to enter cell nuclei for effective chemotherapy. Accompanied by bright far‐red/near‐infrared emission from the PS, image‐guided photo‐chemotherapy with enhanced efficacy is achieved.