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

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Anticancer drug resistance is a large contributing factor to the global mortality rate of cancer patients. Anticancer macromolecules such as polymers were recently reported to overcome this issue. Anticancer macromolecules… Click to show full abstract

Anticancer drug resistance is a large contributing factor to the global mortality rate of cancer patients. Anticancer macromolecules such as polymers were recently reported to overcome this issue. Anticancer macromolecules have unselective toxicity because they are highly positively charged. Herein, an anionic biodegradable polycarbonate carrier was synthesized and utilized to form nanocomplexes with an anticancer polycarbonate via self-assembly to neutralize its positive charges. Biotin was conjugated to the anionic carrier and served as a cancer cell-targeting moiety. The nanoparticles had sizes of <130 nm with anticancer polymer loading levels of 38%-49%. Unlike the small molecular anticancer drug doxorubicin, the nanocomplexes effectively inhibited 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 increased the anticancer polymer's in vivo half-life from 1 h to 6 - 8 h, and rapidly killed BT474 human breast cancer cells primarily via an apoptotic mechanism. The nanocomplexes significantly increased the median lethal dose (LD50) and reduced the injection site toxicity of the anticancer polymer. They suppressed 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. This article is protected by copyright. All rights reserved.

Keywords: toxicity; half; anticancer macromolecules; anticancer; drug; cancer

Journal Title: Advanced healthcare materials
Year Published: 2023

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