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ACS Nano. 2014 Feb 25;8(2):1525-37. doi: 10.1021/nn405724x. Epub 2014 Jan 15.

Bioengineered bacterial outer membrane vesicles as cell-specific drug-delivery vehicles for cancer therapy.

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1
KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST) , 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea.

Abstract

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.

PMID:
24410085
DOI:
10.1021/nn405724x
[Indexed for MEDLINE]

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