Although mortality continues to decline over the past two decades, cancer is still a pervasive healthcare problem worldwide due to the increase in the number of cases, multidrug resistance (MDR) and metastasis. As a consequence of multidrug resistance, a host of chemotherapeutic agents and chemosensitizers have to be used to achieve remission, causing numerous harmful side effects. To overcome these issues, a series of biodegradable cationic polycarbonates has been designed and synthesized as anti-cancer agents. The polymers which were functionalized with quaternary ammonium groups killed cancer cells with different efficiency and killing kinetics as compared to the polymers which functionalized with guanidinium groups. Moreover, they killed cancer cells with different mechanisms. The guanidinium-functionalized polymers which can self-assemble into micellar nanoparticles are highly effective against various cancer cell lines including multidrug-resistant ones. Repeated use of the polymers at sub-lethal doses did not induce resistance. <i>In vivo</i> antitumor efficacy was investigated in a metastatic 4T1 subcutaneous tumor model. Treatment with the polymers a dose of 20 mg/kg of mouse body weight suppressed tumor growth and inhibited tumor metastasis. These polymers show promise in the treatment of cancer without the onset of resistance.

Polymers with distinctive anticancer mechanism that inhibits tumor metastasis and mitigates drug resistance

2019 Fall National Meeting

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