방사선의학 웹진

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Abstract

Achieving accurate and efficacious tumor targeting with minimal off-target effects is of paramount importance in designing diagnostic and therapeutic agents for cancer. In this respect, nanocarriers have gained enormous popularity because of their attainable multifunctional features, as well as tumor-targeting potential by extravasation. However, once administered into the bloodstream, nanocarriers face various in vivo obstacles that may significantly impair their performance needed for clinical translation. Herein, we demonstrate a strategy to enhance tumor-targeting efficiency by embedding functionalities in the interior region of partially PEGylated nanocarriers (ca. 10 nm in diameter), intended for active or passive targeting. The cooperative impact of these topologically inner functional groups (IFGs) was marked: enhancements of >100-fold in IC50in vitro (e.g., a high-avidity ligand with cationic IFGs) and >2-fold in tumor accumulation at 2 h post-injection in vivo (e.g., a high-avidity ligand with anionic IFGs), both against the fully PEGylated counterpart. Analogous to allosteric modulators, properly employed IFGs may substantially improve the process of effectively directing nanocarriers to tumors, which is otherwise solely dependent on avidity or extravasation.

 Author affiliations

Ju Young Heo,ab  Se Hun Kang,c  Young-Hwa Kim,de  Suyeon You,a  Kyeong Sik Jin,f  Seung Won Kim,c  Hye-youn Jung,a  Kyung Oh Jung,de  Chul-Hee Lee,de  Mi Jung Kim,a  Soo-Eun Sung,a  Boram Kim,a  Insung S. Choi,b  Hyewon Youn,deg  June-Key Chung,*deg  Seok-ki Kim*c  and  Yoonkyung Kim*ah ​

* Corresponding authors

a Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea E-mail: ykim@kribb.re.kr

b Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon, Korea

c Molecular Imaging and Therapy Branch, National Cancer Center, Goyang, Korea E-mail: skkim@ncc.re.kr

d Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea E-mail: jkchung@snu.ac.kr

e Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

f Pohang Accelerator Laboratory, Pohang University of Science and Technology, Pohang, Korea

g Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea

h Korea University of Science and Technology (UST), Daejeon, Korea