A Comparison of Di- and Trinuclear Platinum Complexes Interacting with Glycosaminoglycans for Targeted Chemotherapy

Overview

Journal ACS Med Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2023 Sep 22

PMID 37736178

Authors

Samantha J Katner

Eric P Ginsburg

James D Hampton

Erica J Peterson

Jennifer E Koblinski

Nicholas P Farrell

Affiliations

Soon will be listed here.

Abstract

Heparan sulfate proteoglycans (HSPGs) and their associated proteins aid in tumor progression through modulation of biological events such as cell invasion, angiogenesis, metastasis, and immunological responses. Metalloshielding of the anionic heparan sulfate (HS) chains by cationic polynuclear platinum complexes (PPCs) prevents the HS from interacting with HS-associated proteins and thus diminishes the critical functions of HSPG. Studies herein exploring the PPC-HS interactions demonstrated that a series of PPCs varying in charge, nuclearity, distance between Pt centers, and hydrogen-bonding ability influence HS affinity. We report that the polyamine-linked complexes have high HS affinity and display excellent activity against breast cancer metastases and those arising in the bone and liver compared to carboplatin. Overall, the PPC-HS niche offers an attractive approach for targeting HSPG-expressing tumor cells.

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