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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.

Author information

​Lee JJ1, Kang JA2, Ryu Y1, Han SS3, Nam YR2, Rho JK2, Choi DS2, Kang SW4, Lee DE5, Kim HS6.​

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.