期刊
ACS NANO
卷 8, 期 2, 页码 1525-1537出版社
AMER CHEMICAL SOC
DOI: 10.1021/nn405724x
关键词
affibody; cancer therapy; drug delivery; outer membrane vesicles; siRNA
类别
资金
- Bio & Medical Technology Development Program of the National Research Foundation [2013035952]
- Intelligent Synthetic Biology Center of Global Frontier Project
- Ministry of Science, ICT & Future Planning [2013M3A6A8073557]
Advances in genetic engineering tools have contributed to the development of strategies for utilizing biologically derived vesicles as nanomedicines for achieving cell-specific drug delivery. Here, we describe bioengineered bacterial outer membrane vesicles (OMVs) with low immunogenicity that can target and kill cancer cells in a cell-specific manner by delivering small interfering RNA (siRNA) targeting kinesin spindle protein (KSP). A mutant Escherichia coli strain that exhibits reduced endotoxicity toward human cells was engineered to generate OMVs displaying a human epidermal growth factor receptor 2 (HER2)-specific affibody in the membrane as a targeting ligand. Systemic injection of siRNA-packaged OMVs caused targeted gene silencing and induced highly significant tumor growth regression in an animal model. Importantly, the modified OMVs were well tolerated and showed no evidence of nonspecific side effects. We propose that bioengineered OMVs have great potential as cell-specific drug-delivery vehicles for treating various cancers.
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