Click chemistry-mediated tumor-targeting of SN38-loaded nanoparticles using trastuzumab.

Affiliation

Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea; Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea; Catholic Photomedicine Research Institute, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea. Electronic address: [Email]

Abstract

For efficient drug delivery, we introduce a click-chemistry-mediated two-step tumor-targeting strategy for nanoparticles (NPs). We modified HER2-binding trastuzumab with trans-cyclooctene (TCO-Trb), and fabricated tetrazine-modified NPs containing the anticancer drug, SN38 (SN38-Tz-NPs). To target tumor cells with the Tz-NPs, the tumor cells are first treated with TCO-Trb. The TCO-Trb binds HER2s and presents multiple TCO groups on the cell surface. Subsequently, the cells are treated with SN38-Tz-NPs that can bind the cell surface via click chemistry between Tz and TCO. This click chemistry-mediated binding resulted in enhanced tumor-targeting of Tz-NPs to the target tumor cells. In our study, this strategy was performed and analyzed in vitro and in vivo, and the results show that this is a promising strategy for tumor-targeted drug delivery by NPs.

Keywords

Click chemistry,Drug delivery,In vivo imaging,Nanoparticle,SN38,Trastuzumab,

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