Design of Highly Selective Zn-Coordinated Polyampholyte for Cancer Treatment and Inhibition of Tumor Metastasis

Developing anticancer agents with negligible cytotoxicity against normal cells while mitigating multidrug resistance and metastasis is challenging. Previously reported cationic polymers have effectively eradicated cancers but are clinically unsuitable due to their limited selectivity. Herein, a series of poly(l-lysine)- and nicotinic acid-based polymers were synthesized using varying amounts of dodecylsuccinic anhydride. Zn-coordinating polymers concealed their cationic charge and enhanced selectivity. These Zn-bound polymers were highly effective against liver and colon cancer cells (HepG2 and Colon 26, respectively) and prevented cancer cell migration. They also displayed potent anticancer activity against drug-resistant cell lines (COR-L23/R): their cationic structure facilitated cancer cell membrane disruption. Compared to these polymers, doxorubicin was less selective and less efficacious against drug-resistant cell lines and was unable to prevent cell migration. These polymers are potential cancer treatment agents, offering a promising solution for mitigating drug resistance and tumor metastasis and representing a novel approach to designing cancer therapeutics.