Yoon, Hong Yeol Shin, Mm Lee Shim, Man Kyu Lee, Sangmin Na, Jin Hee Koo, Heebeom Lee, Hyukjin Kim, Jong-Ho Lee, Kuen Yong Kim, Kwangmeyung Kwon, Ick Chan 2024-01-20T01:33:21Z 2024-01-20T01:33:21Z 2021-09-01 2017-05 1543-8384 https://pubs.kist.re.kr/handle/201004/122805 Biological ligands such as aptamer, antibody, glucose, and peptide have been widely used to bind specific surface molecules or receptors in tumor cells or subcellular structures to improve tumor-targeting efficiency of nanoparticles. However, this active-targeting strategy has limitations for tumor targeting due to inter- and intraheterogeneity of tumors. In this study, we demonstrated an alternative active-targeting strategy using metabolic engineering and bioorthogonal click reaction to improve tumor-targeting efficiency of nanoparticles. We observed that azide-containing chemical reporters were successfully generated onto surface glycans of various tumor cells such as lung cancer (A549), brain cancer (U87), and breast cancer (BT-474, MDA-MB231, MCF-7) via metabolic engineering in vitro. In addition, we compared tumor targeting-of artificial azide reporter with bicyclononyne (BCN)-conjugated glycol chitosan nanoparticles (BCN-CNPs) and integrin alpha(v)beta(3) with cyclic RGD-conjugated CNPs (cRGD-CNPs) in vitro and in vivo. Fluorescence intensity of azide-reporter-targeted BCN-CNPs in tumor tissues was 1.6-fold higher and with a more uniform distribution compared to that of cRGD-CNPs. Moreover, even in the isolated heterogeneous U87 cells, BCN-CNPs could bind artificial azide reporters on tumor cells more unifornaly (similar to 92.9%) compared to cRGD-CNPs. Therefore, the artificial azide-reporter-targeting strategy can be utilized for targeting heterogeneous tumor cells via bioorthogonal click reaction and may provide an alternative method of tumor targeting for further investigation in cancer therapy. English AMER CHEMICAL SOC Artificial Chemical Reporter Targeting Strategy Using Bioorthogonal Click Reaction for Improving Active-Targeting Efficiency of Tumor Article 10.1021/acs.molpharmaceut.6b01083 1 MOLECULAR PHARMACEUTICS, v.14, no.5, pp.1558 - 1570 MOLECULAR PHARMACEUTICS 14 5 1558 1570 N scie scopus 000400633300023 2-s2.0-85018370929 Medicine, Research & Experimental Pharmacology & Pharmacy Research & Experimental Medicine Pharmacology & Pharmacy Article IN-VIVO DRUG-DELIVERY CLINICAL-IMPLICATIONS SIALIC-ACID CANCER NANOPARTICLES HETEROGENEITY CHEMISTRY PROTEINS THERAPEUTICS metabolic glycoengineering bioorthogonal click reaction active tumor targeting heterogeneity