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.