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

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.

• Authors: Jihye Yoo, Sangkee Choi, Jihwan Son, Gawon Yi, Eunha Kim, Heebeom Koo
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 515 Issue 1 Pg. 207-213 (07 12 2019) ISSN: 1090-2104 [Electronic] United States
• PMID: 31146921 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Cyclooctanes
• Topoisomerase I Inhibitors
• Irinotecan
• Receptor, ErbB-2
• Trastuzumab

Topics

• Animals
• Cell Line, Tumor
• Click Chemistry (methods)
• Cyclooctanes (chemistry)
• Drug Delivery Systems (methods)
• Irinotecan (administration & dosage, chemistry, pharmacokinetics)
• Mice, Inbred BALB C
• Mice, Nude
• Nanoparticles (administration & dosage, chemistry)
• Neoplasms, Experimental (drug therapy, metabolism, pathology)
• Protein Binding
• Receptor, ErbB-2 (genetics, metabolism)
• Tissue Distribution
• Topoisomerase I Inhibitors (administration & dosage, chemistry, pharmacokinetics)
• Trastuzumab (administration & dosage, chemistry, metabolism, pharmacokinetics)