Addressing Drug Resistance in Cancer with Macromolecular Chemotherapeutic Agents
In: Journal of the American Chemical Society, Jg. 140 (2018-03-06), Heft 12
Online
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Zugriff:
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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Addressing Drug Resistance in Cancer with Macromolecular Chemotherapeutic Agents
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Autor/in / Beteiligte Person: | Bianco, Simone ; Hedrick, James L. ; Periaswamy, Balamurugan ; Liu, Shaoqiong ; Park, Nathaniel H. ; Chen, Qingfeng ; Paola Florez de Sessions ; Yi Yan Yang ; Yang, Chuan ; Lai, Fritz ; Collins Wenhan Chu ; Venkataraman, Shrinivas ; Cheng, Wei |
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Zeitschrift: | Journal of the American Chemical Society, Jg. 140 (2018-03-06), Heft 12 |
Veröffentlichung: | 2018 |
Medientyp: | unknown |
ISSN: | 1520-5126 (print) |
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