期刊
ADVANCED HEALTHCARE MATERIALS
卷 8, 期 16, 页码 -出版社
WILEY
DOI: 10.1002/adhm.201900500
关键词
cancer therapy; polymersomes; polypeptides; small interfering RNA (siRNA); targeted delivery
资金
- National Natural Science Foundation of China [NSFC 51773145, 51761135117, 51633005, 51473110] Funding Source: Medline
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.
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