Nanocomplexes of Biodegradable Anticancer Macromolecules: Prolonged Plasma Half-Life, Reduced Toxicity, and Increased Tumor Targeting

Abstract

Anticancer drug resistance is a large contributing factor to the global mortality rate of cancer patients. Anticancer macromolecules such as polymers have been recently reported to overcome this issue. Anticancer macromolecules have unselective toxicity because they are highly positively charged. Herein, an anionic biodegradable polycarbonate carrier is synthesized and utilized to form nanocomplexes with an anticancer polycarbonate via self-assembly to neutralize its positive charges. Biotin is conjugated to the anionic carrier and serves as cancer cell-targeting moiety. The nanoparticles have sizes of < 130 nm with anticancer polymer loading levels of 38–49%. Unlike the small molecular anticancer drug doxorubicin, the nanocomplexes effectively inhibit the growth of both drug-susceptible MCF7 and drug-resistant MCF7/ADR human breast cancer cell lines with low half maximal inhibitory concentration (IC50). The nanocomplexes increase the anticancer polymer's in vivo half-life from 1 to 6–8 h, and rapidly kill BT474 human breast cancer cells primarily via an apoptotic mechanism. The nanocomplexes significantly increase the median lethal dose (LD50) and reduce the injection site toxicity of the anticancer polymer. They suppress tumor growth by 32–56% without causing any damage to the liver and kidneys. These nanocomplexes may potentially be used for cancer treatment to overcome drug resistance.