Selective Cell Penetrating Peptide-Functionalized Envelope-Type Chimeric Lipopepsomes Boost Systemic RNAi Therapy for Lung Tumors
Min Qiu1, Jia Ouyang2, Yaohua Wei1, Jian Zhang1, Qing Lan2, Chao Deng1,*（邓超）, and Zhiyuan Zhong1,*（钟志远）
1Biomedical Polymers Laboratory Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application College of Chemistry
Chemical Engineering and Materials Science and State Key Laboratory of Radiation Medicine and Protection Soochow University Suzhou 215123, China
2Department of Neurosurgery The Second Affiliated Hospital of Soochow University Suzhou 215123, China
Adv. Healthcare Mater. 2019, 1900500
Small interfering RNA (siRNA) is considered a highly specific and potent
biotherapeutic that holds tremendous potential for the treatment of various diseases. The clinical translation of siRNA is, however, greatly impeded by the lack of safe and efficient delivery vehicles in vivo. Here, the development of selective cell penetrating peptide (CPP33)-functionalized chimeric lipopepsomes (CPP33-CLP) for efficient encapsulation and selective delivery of polo-like kinase 1 specific siRNA (siPLK1) to orthotopic A549 human lung tumor in vivo is reported. Interestingly, siRNA is tightly encapsulated into CPP33-CLP with a superb encapsulation efficiency of over 95% owing to the thick strong electrostatic interactions. Notably, siPLK1-loaded CPP33-CLP (siPLK1-CPP33-CLP) is selectively internalized by A549 human lung cancer
cells, efficiently escapes from endosomes, and swiftly releases siRNA into the cytoplasm, affording a significant sequence-specific gene silencing in vitro. Moreover, siPLK1-CPP33-CLP exhibits prolonged blood circulation, enhanced tumor accumulation, effective suppression of tumor growth, and considerably elevated survival time of orthotopic A549 human lung tumor-bearing nude mice. These chimeric lipopepsomes appear as an attractive and potent nanoplatform for safe and targeted siRNA delivery.
链接：https://onlinelibrary.wiley.com/doi/abs/10.1002/adhm.201900500