Disassembly of Hydrophobic Photosensitizer by Biodegradable Zeolitic Imidazolate Framework‑8 for Photodynamic Cancer Therapy

Photodynamic therapy (PDT), an alternative to conventional cancer therapeutics, has gained increasing attention for its noninvasive advantage and simultaneous fluorescence imaging property. PDT is a tripartite process that functions in the simultaneous presence of a photosensitizer (PS), light, and available oxygen molecules. However, many highly efficient PSs are hydrophobic and highly tend to self-aggregate in aqueous solution, leading to quick quenching of the PDT effect. Here we construct zeolitic imidazolate framework-8 (ZIF-8) containing water-insoluble photosensitizer zinc­(II) phthalocyanine (ZnPc), a typical hydrophobic PS, by one-step coprecipitation process, named as ZnPc@ZIF-8. The micropores of ZIF-8 act as molecular cages to separate and maintain hydrophobic ZnPc in the monomeric state and protect it against self-aggregation, which enables the encapsulated ZnPc to generate cytotoxic singlet oxygen (¹O₂) under light irradiation (650 nm) in aqueous condition. The formed nanosystem of ZnPc@ZIF-8 can be endocytosed by cancer cells and exhibits red fluorescent emission with excellent photodynamic activity for cancer treatment <i>in vitro</i>. In addition, ZnPc@ZIF-8 is acid-sensitive and would completely degrade after PDT, which can be monitored by the self-quenching of fluorescence emission of ZnPc. This work paves a facile way for resolving the problem of solubility and bioavailability of hydrophobic PS by utilizing metal–organic frameworks as nanocarriers