Polymeric Copper Chelator for Long-term Inhibition of Breast Cancer Proliferation and Lung Metastasis

Breast cancer is the deadliest cancer among women worldwide. Copper chelation therapy has made remarkable achievements in inhibiting the proliferation and metastasis of breast cancer. However, the low bioavailability of small-molecule copper chelators causes poor or ineffective cancer inhibition. This study developed safe and long-lasting polymeric copper chelators by combining the tricomponent Kabachnik-Fields reaction, hydroxyquinoline, and controlled radical polymerization. Water-soluble polymers with controlled molecular weights, biosafety, and excellent copper-chelating ability were prepared. During in vivo experiments, these polymeric chelators were superior in effectively inhibiting lung metastasis compared with tetrathiomolybdate, which is the only copper-chelating medicine applied in clinical trials. The polymer with a higher molecular weight had a longer metabolic time and, therefore, exhibited a better long-term inhibition of cancer metastasis. This is an initial attempt to investigate well-defined polymeric copper chelators via multicomponent reactions and polymer chemistry. This study provides underlying insights to guide the design of anticancer polymers for biomedical applications.