Man Kyu Shim1,4,†, Dr. Hong Yeol Yoon1,3,†, Dr. Ju Hee Ryu1, Dr. Heebeom Koo2, Dr. Sangmin Lee1,5, Dr. Jae Hyung Park3, Dr. Jong-Ho Kim4, Dr. Seulki Lee5, Dr. Martin G. Pomper5, Dr. Ick Chan Kwon1,6 and Dr. Kwangmeyung Kim1,*
1Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seongbuk-gu, Seoul, Republic of Korea
2Department of Medical Life Science, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul, Republic of Korea
3School of Chemical Engineering, Sungkyunkwan University, Jangan-gu, Suwon, Republic of Korea
4Department of Pharmacy, Graduate School, Kyung Hee University, Dongdaemun-gu, Seoul, Republic of Korea
5The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
6KU-KIST Graduate School of Converging Science and Technology, Korea University, Seongbuk-gu, Seoul, Republic of Korea
†These authors contributed equally to this work.
Recently, metabolic glycoengineering with bioorthogonal click reactions has focused on improving the tumor targeting efficiency of nanoparticles as delivery vehicles for anticancer drugs or imaging agents. It is the key technique for developing tumor-specific metabolic precursors that can generate unnatural glycans on the tumor-cell surface. A cathepsin B-specific cleavable substrate (KGRR) conjugated with triacetylated N-azidoacetyl-d-mannosamine (RR-S-Ac3ManNAz) was developed to enable tumor cells to generate unnatural glycans that contain azide groups. The generation of azide groups on the tumor cell surface was exogenously and specifically controlled by the amount of RR-S-Ac3ManNAz that was fed to target tumor cells. Moreover, unnatural glycans on the tumor cell surface were conjugated with near infrared fluorescence (NIRF) dye-labeled molecules by a bioorthogonal click reaction in cell cultures and in tumor-bearing mice. Therefore, our RR-S-Ac3ManNAz is promising for research in tumor-specific imaging or drug delivery.