Cancer Cell-Targeted Photosensitizer and Therapeutic Protein Co-Delivery Nanoplatform Based on a Metal–Organic Framework for Enhanced Synergistic Photodynamic and Protein Therapy

Efficient and cancer cell-targeted delivery of photosensitizer (PS) and therapeutic protein has great potentiality for improving the anticancer effects. Herein, zeolitic imidazolate framework-8 (ZIF-8) nanoparticles, one of the most attractive metal–organic framework materials, were used for coencapsulating the chlorin e6 (Ce6, a potent PS) and cytochrome c (Cyt c, a protein apoptosis inducer); then the nanoparticle was subsequently decorated with the hyaluronic acid (HA) shell to form cancer cell-active targeted nanoplatform (Ce6/Cyt c@ZIF-8/HA). The in vitro and in vivo experiments show the cancer cell targeting capability and pH-responsive decomposition and the release behavior of Ce6/Cyt c@ZIF-8/HA. Upon light irradiation, the released Ce6 produced cytotoxic reactive oxygen species for photodynamic therapy. Meanwhile, the released Cyt c-induced programmed cell death for protein therapy. Furthermore, the Cyt c worked normally under hypoxia conditions and could decompose H₂O₂ to O₂ (with peroxidase-/catalase-like activity), resulting in synergistically improved therapeutic efficiency. These small molecules and protein codelivery nanoplatforms would promote the development of complementary and synergetic modes for biomedical applications.