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

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

Advanced Healthcare Materials

10.1002/adhm.202201560

http://dx.doi.org/10.1002/adhm.202201560

Jiayu Leong, Joyce Tay, Shengcai Yang, Chuan Yang, Eddy Wei Ping Tan, Yanming Wang, Bing Qian Tan, Sherwin Hor, Yau Hong Chua, Jeremy Pang Kern Tan, Qingfeng Chen, James L. Hedrick, Yi Yan Yang

Biomaterials, Pharmaceutical Science, Biomedical engineering

18 April 2023

Leong, J., Tay, J., Yang, S., Yang, C., Tan, E. W. P., Wang, Y., Tan, B. Q., Hor, S., Chua, Y. H., Tan, J. P. K., Chen, Q., Hedrick, J. L., & Yang, Y. Y. (2023). Nanocomplexes of Biodegradable Anticancer Macromolecules: Prolonged Plasma Half‐Life, Reduced Toxicity, and Increased Tumor Targeting. Advanced Healthcare Materials. Portico. https://doi.org/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 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 <130nm 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 1h to 6 - 8h, 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.

Publisher Copyright

This research is supported by core funding from: BMRC, A*STAR
Grant Reference no. : UIBR

This is the peer reviewed version of the following article: Leong, J., Tay, J., Yang, S., Yang, C., Tan, E. W. P., Wang, Y., Tan, B. Q., Hor, S., Chua, Y. H., Tan, J. P. K., Chen, Q., Hedrick, J. L., & Yang, Y. Y. (2023). Nanocomplexes of Biodegradable Anticancer Macromolecules: Prolonged Plasma Half‐life, Reduced Toxicity, and Increased Tumor Targeting. Advanced Healthcare Materials. Portico. https://doi.org/10.1002/adhm.202201560, which has been published in final form at doi.org/10.1002/adhm.202201560. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.

https://oar.a-star.edu.sg/communities-collections/articles/19052

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Bioprocessing Technology Institute