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

• Published in: Advanced healthcare materials 2023-07, Vol.12 (19), p.e2201560-n/a
• Main Authors: Leong, Jiayu, Tay, Joyce, Yang, Shengcai, Yang, Chuan, Tan, Eddy Wei Ping, Wang, Yanming, Tan, Bing Qian, Hor, Sherwin, Chua, Yau Hong, Tan, Jeremy Pang Kern, Chen, Qingfeng, Hedrick, James L., Yang, Yi Yan
• Format: Article
• Language: English
• Subjects: anticancer macromolecule; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Antitumor agents; Apoptosis; Biocompatibility; Biodegradability; Biotin; Breast cancer; Breast Neoplasms - drug therapy; Cancer therapies; Doxorubicin; Doxorubicin - pharmacology; Drug resistance; Female; Half-Life; Humans; Lethal dose; Macromolecules; Nanoparticles; Nanoparticles - toxicity; Polycarbonate; Polycarbonate resins; polycarbonates; polymeric nanocomplexes; Polymers; Self-assembly; supramolecular assembly; Toxicity; Tumor cell lines; Tumors
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.202201560

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. Unlike small molecular anticancer drugs, the biotin‐functionalized anticancer nanocomplexes effectively inhibit the growth of both drug‐susceptible and drug‐resistant cancers via apoptosis with low effective concentrations. They significantly reduce toxicity and prolong blood circulation of anticancer polycarbonate and suppressed tumor growth without causing any damage to major organs. These nanocomplexes may potentially be used for cancer treatment to overcome drug resistance.