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

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• 作者：Joong-jae Lee^a ; ¹ ; Jung Ae Kang^b ; ¹ ; Yiseul Ryu^a ; Sang-Soo Han^c ; You Ree Nam^b ; Jong Kook Rho^b ; Dae Seong Choi^b ; Sun-Woong Kang^c ; ^d ; Dong-Eun Lee^b ; ^{delee@kaeri.re.kr} ; Hak-Sung Kim^a ; ^{hskim76@kaist.ac.kr}
• 关键词：Targeted delivery ; Cancer therapy ; Tumour selectivity ; Protein nanoparticle ; Repebody ; Self-assembly
• 刊名：Biomaterials
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：120
• 期：Complete
• 页码：22-31
• 全文大小：1775 K
• 卷排序：120

文摘

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.