| Literature DB >> 29504396 |
Nathaniel H Park1, Wei Cheng2, Fritz Lai3, Chuan Yang2, Paola Florez de Sessions4, Balamurugan Periaswamy4, Collins Wenhan Chu4, Simone Bianco1, Shaoqiong Liu2, Shrinivas Venkataraman2, Qingfeng Chen3, Yi Yan Yang2, James L Hedrick1.
Abstract
Drug resistance to chemotherapeutics is a recurrent issue plaguing many cancer treatment regimens. To circumvent resistance issues, we have designed a new class of macromolecules as self-contained chemotherapeutic agents. The macromolecular chemotherapeutic agents readily self-assemble into well-defined nanoparticles and show excellent activity in vitro against multiple cancer cell lines. These cationic polymers function by selectively binding and lysing cancer cell membranes. As a consequence of this mechanism, they exhibit significant potency against drug-resistant cancer cells and cancer stem cells, prevent cancer cell migration, and do not induce resistance onset following multiple treatment passages. Concurrent experiments with the small-molecule chemotherapeutic, doxorubicin, show aggressive resistance onset in cancer cells, a lack of efficacy against drug-resistant cancer cell lines, and a failure to prevent cancer cell migration. Additionally, the polymers showed anticancer efficacy in a hepatocellular carcinoma patient derived xenograft mouse model. Overall, these results demonstrate a new approach to designing anticancer therapeutics utilizing macromolecular compounds.Entities:
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Year: 2018 PMID： 29504396 DOI： 10.1021/jacs.7b11468
Source DB: PubMed Journal: J Am Chem Soc ISSN： 0002-7863 Impact factor: 15.419