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

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Abstract
Efficient and cancer cell targeted delivery of photosensitizer (PS) and therapeutic protein have great potentiality for improving the anticancer effects. Herein, zeolitic imidazolate framework-8 (ZIF-8) nanoparticle, one of the most attractive metal-organic framework materials, was used for co-encapsulating the chlorin e6 (Ce6, a potent PS) and cytochrome c (Cyt c, a protein apoptosis inducer), then the nanoparticle was subsequently decorated with hyaluronic acid (HA) shell to form cancer cell active targeted nanoplatform (Ce6/Cyt [email protected]/HA). The in vitro and in vivo experiments show the cancer cell targeting capability and pH-responsive decomposition and release behavior of Ce6/Cyt [email protected]/HA. Upon light irradiation, the released Ce6 produced cytotoxic reactive oxygen species (ROS) for photodynamic therapy. Meanwhile, the released Cyt c induced programmed cell death for protein therapy. Furthermore, the Cyt c worked normally under hypoxia condition and could decompose H2O2 to O2 (with peroxidase/catalase like activity), resulting in synergistically improved therapeutic efficiency. These small molecules and protein co-delivery nanoplatforms would promote the development of complementary and synergetic modes for biomedical applications.
Funding Information
  • China Postdoctoral Science Foundation (2019M652241)
  • National Natural Science Foundation of China (21605021, 61875141)
  • Fujian Provincial Health Commission (2019-WJ-12)
  • Fujian Province (2018-CX-49, 2018Y9119)
  • Education Commission of Fujian Province (2019-WJ-12)

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