Cancer Cell-Targeted Photosensitizer and Therapeutic Protein Co-Delivery Nanoplatform Based on a Metal–Organic Framework for Enhanced Synergistic Photodynamic and Protein Therapy
Lei Ding, Xiao Lin, Ziguo Lin, Yanni Wu, Xiaolong Liu, Jingfeng Liu, Ming Wu, Xiaolong Zhang, Yongyi Zeng
Abstract
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.