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

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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. (C) 2016 Elsevier Ltd. All rights reserved.
Publisher
ELSEVIER SCI LTD
Issue Date
2017-03
Language
English
Article Type
Article
Keywords

CHICKEN ANEMIA VIRUS; TUMOR-CELLS; IN-VITRO; APOPTIN; DELIVERY; APOPTOSIS; ANTIBODY; DRUGS; EGFR; VIVO

Citation

BIOMATERIALS, v.120, pp.22 - 31

ISSN
0142-9612
DOI
10.1016/j.biomaterials.2016.12.014
URI
http://hdl.handle.net/10203/222697
Appears in Collection
BS-Journal Papers(저널논문)
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