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Lee, Joong-jae,Kang, Jung Ae,Ryu, Yiseul,Han, Sang-Soo,Nam, You Ree,Rho, Jong Kook,Choi, Dae Seong,Kang, Sun-Woong,Lee, Dong-Eun,Kim, Hak-Sung IPC Science and Technology Press 2017 Biomaterials Vol.120 No.-
<P><B>Abstract</B></P> <P>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 <I>E. coli</I>, 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 <I>E. coli</I>. 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.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>