In situ generated D-peptidic nanofibrils as multifaceted apoptotic inducers to target cancer cells

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dc.contributor.author Du, Xuewen
dc.contributor.author Zhou, Jie
dc.contributor.author Wang, Huainin
dc.contributor.author Shi, Junfeng
dc.contributor.author Kuang, Yi
dc.contributor.author Zeng, Wu
dc.contributor.author Yang, Zhimou
dc.contributor.author Xu, Bing
dc.date.accessioned 2017-10-31T15:55:36Z
dc.date.available 2017-10-31T15:55:36Z
dc.date.issued 2016-11-30
dc.identifier.citation Cell Death and Disease (2017) 8, e2614 https://www.nature.com/cddis/journal/v8/n2/full/cddis2016466a.html
dc.identifier.uri http://hdl.handle.net/10192/34675
dc.description Published article can be found at: https://www.nature.com/cddis/journal/v8/n2/full/cddis2016466a.html
dc.description.abstract Nanofibrils of small molecules, as a new class of biofunctional entities, exhibit emergent properties for controlling cell fates, but the relevant mechanism remains to be elucidated and the in vivo effect has yet to be examined. Here, we show that D-peptide nanofibrils, generated by enzyme-instructed self-assembly (EISA), pleiotropically activate extrinsic death signaling for selectively killing cancer cells. Catalyzed by alkaline phosphatases and formed in situ on cancer cells, D-peptide nanofibrils present autocrine proapoptotic ligands to their cognate receptors in a juxtacrine manner, as well as directly cluster the death receptors. As multifaceted initiators, D peptide nanofibrils induce apoptosis of cancer cells without harming normal cells in a co-culture, kill multidrug-resistant (MDR) cancer cells, boost the activities of anticancer drugs, and inhibit tumor growth in a murine model. Such a supramolecular cellular biochemical process (consisting of reaction, assembly, and binding) for multi-targeting or modulating protein–protein interaction networks ultimately may lead to new ways for combating cancer drug resistance.
dc.description.sponsorship Funded by the Brandeis University Open Access Fund
dc.language English
dc.language.iso eng
dc.publisher Nature Publishing Group
dc.rights Copyright by authors 2016
dc.subject In vivo
dc.subject EISA
dc.subject Nanofibrils
dc.title In situ generated D-peptidic nanofibrils as multifaceted apoptotic inducers to target cancer cells
dc.type Article
dc.identifier.doi http://dx.doi.org/10.1038/cddis.2016.466


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