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Biomaterials. 2017 Mar;120:22-31. doi: 10.1016/j.biomaterials.2016.12.014. Epub 2016 Dec 19.

Genetically engineered and self-assembled oncolytic protein nanoparticles for targeted cancer therapy.

Author information

1
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, South Korea.
2
Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute (KAERI), Jeongeup, Jeonbuk 580-185, South Korea.
3
Predictive Model Research Center, Korea Institute of Toxicology (KIT), Daejeon 34114, South Korea.
4
Predictive Model Research Center, Korea Institute of Toxicology (KIT), Daejeon 34114, South Korea; Department of Human and Environmental Toxicology, University of Science and Technology (UST), Daejeon 34113, South Korea.
5
Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute (KAERI), Jeongeup, Jeonbuk 580-185, South Korea. Electronic address: delee@kaeri.re.kr.
6
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, South Korea. Electronic address: hskim76@kaist.ac.kr.

Abstract

The integration of a targeted delivery with a tumour-selective agent has been considered an ideal platform for achieving high therapeutic efficacy and negligible side effects in cancer therapy. Here, we present engineered protein nanoparticles comprising a tumour-selective oncolytic protein and a targeting moiety as a new format for the targeted cancer therapy. Apoptin from chicken anaemia virus (CAV) was used as a tumour-selective apoptotic protein. An EGFR-specific repebody, which is composed of LRR (Leucine-rich repeat) modules, was employed to play a dual role as a tumour-targeting moiety and a fusion partner for producing apoptin nanoparticles in E. coli, respectively. The repebody was genetically fused to apoptin, and the resulting fusion protein was shown to self-assemble into supramolecular repebody-apoptin nanoparticles with high homogeneity and stability as a soluble form when expressed in E. coli. The repebody-apoptin nanoparticles showed a remarkable anti-tumour activity with negligible side effects in xenograft mice through a cooperative action of the two protein components with distinct functional roles. The repebody-apoptin nanoparticles can be developed as a systemic injectable and tumour-selective therapeutic protein for targeted cancer treatment.

KEYWORDS:

Cancer therapy; Protein nanoparticle; Repebody; Self-assembly; Targeted delivery; Tumour selectivity

[Indexed for MEDLINE]

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