期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 140, 期 12, 页码 4244-4252出版社
AMER CHEMICAL SOC
DOI: 10.1021/jacs.7b11468
关键词
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资金
- IBM Research-Almaden
- Institute of Bioengineering and Nanotechnology (Biomedical Research Council, Agency for Science, Technology and Research, Singapore)
- National Medical Research Council (NMRC), Singapore [NMRC/TCR/014-NUHS/2015]
- Singapore National Research Foundation Fellowship [NRF-NRFF2017-03]
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.
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