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

Samantha J Katner; Eric P Ginsburg; James D Hampton; Erica J Peterson; Jennifer E Koblinski; Nicholas P Farrell

doi:10.1021/acsmedchemlett.3c00244

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

ACS Med Chem Lett. 2023 Sep 1;14(9):1224-1230. doi: 10.1021/acsmedchemlett.3c00244. eCollection 2023 Sep 14.

Authors

Samantha J Katner¹, Eric P Ginsburg², James D Hampton^{2

3}, Erica J Peterson^{2

3}, Jennifer E Koblinski^{3

4}, Nicholas P Farrell^{2

3}

Affiliations

¹ Department of Biochemistry, Chemistry, and Geology, Minnesota State University, Mankato, Mankato, Minnesota 56001, United States.
² Department of Chemistry, Virginia Commonwealth University, Richmond, Virginia 23284, United States.
³ Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia 23298, United States.
⁴ Department of Pathology, Virginia Commonwealth University, Richmond, Virginia 23298, United States.

PMID: 37736178
PMCID: PMC10510529 (available on 2024-09-14)
DOI: 10.1021/acsmedchemlett.3c00244

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 in vivo 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.