Overcoming Ovarian Cancer Drug Resistance with a Cold Responsive Nanomaterial
Date
2018Journal
ACS Central SciencePublisher
American Chemical SocietyType
Article
Metadata
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Drug resistance due to overexpression of membrane transporters in cancer cells and the existence of cancer stem cells (CSCs) is a major hurdle to effective and safe cancer chemotherapy. Nanoparticles have been explored to overcome cancer drug resistance. However, drug slowly released from nanoparticles can still be efficiently pumped out of drug-resistant cells. Here, a hybrid nanoparticle of phospholipid and polymers is developed to achieve cold-triggered burst release of encapsulated drug. With ice cooling to below ∼12 °C for both burst drug release and reduced membrane transporter activity, binding of the drug with its target in drug-resistant cells is evident, while it is minimal in the cells kept at 37 °C. Moreover, targeted drug delivery with the cold-responsive nanoparticles in combination with ice cooling not only can effectively kill drug-resistant ovarian cancer cells and their CSCs in vitro but also destroy both subcutaneous and orthotopic ovarian tumors in vivo with no evident systemic toxicity. Copyright Copyright 2018 American Chemical Society.Sponsors
This work was partially supported by American Cancer Society (#120936-RSG-11-109-01-CDD) and NIH (R01CA206366).Identifier to cite or link to this item
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85047553075&doi=10.1021%2facscentsci.8b00050&partnerID=40&md5=d84322b89d42a213eea5f0c43f93c67e; http://hdl.handle.net/10713/9304ae974a485f413a2113503eed53cd6c53
10.1021/acscentsci.8b00050