Journal
BIOMATERIALS SCIENCE
Volume 8, Issue 17, Pages 4841-4851Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/d0bm00778a
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Funding
- National Natural Science Foundation of China [31971269, 21727817, 11621505, 31670976, 11875267]
- Natural Science Foundation of Beijing Municipality [7202238]
- Program for High Level Innovative Team Building of Beijing Municipality [IDHT20180504]
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Traditional photodynamic therapy (PDT) requires external light excitation to produce reactive oxygen species (ROSs) for the treatment of tumors. Due to problems of light penetration, traditional PDT is limited by the location and depth of the tumor. In this study, we rationally designed and constructed a novel strategy to amplify the therapeutic effect of PDT. We prepared a chlorin-lipid nanovesicle based on the conjugates of chlorin e6 (Ce 6) and phospholipids, with the surface conjugating the aptamer for lung cancer targeting, GLT21.T.I-131-labeled bovine serum albumin (I-131-BSA) was loaded into the chlorin-lipid nanovesicle cavity (I-131-BSA@LCN-Apt).I-131 not only plays a role in radiotherapy, but its Cerenkov radiation (CR), as an internal light source, can also stimulate Ce6 to produce ROSs without external light excitation. Thein vitroandin vivotherapeutic effects in subcutaneous lung tumor models and orthotopic lung tumor models indicated that(131)I-BSA@LCN-Apt produced a powerful anti-tumor effect through synergistic radiotherapy and CR-PDT, which almost caused complete tumor growth regression. After treatment, the survival time of the mice was significantly prolonged. During the treatment, no obvious side effects were found by histopathology of important organs, hematology and biochemistry analysis except the decrease of the white blood cell count (WBC). The study provides a major tool for deep-seated tumors to obtain amplified therapeutic effects by synergistic radiotherapy and CR-PDT without the use of any external light source.
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