Original Article

Citation: Cell Death and Disease (2017) 8, e2614; doi:10.1038/cddis.2016.466
Published online 16 February 2017

In situ generated Dpeptidic nanofibrils as multifaceted apoptotic inducers to target cancer cells
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Xuewen Du1, Jie Zhou1, Huainin Wang1, Junfeng Shi1, Yi Kuang1, Wu Zeng2, Zhimou Yang3 and Bing Xu1

  1. 1Department of Chemistry, Brandeis University, Waltham, MA 02454, USA
  2. 2The Heller School for Social Policy and Management, Brandeis University, Waltham, MA 02454, USA
  3. 3The College of Life Sciences, Nankai University, Tianjin 300071, China

Correspondence: B Xu, Department of Chemistry, Brandeis University, 415 South Street, Waltham, MA 02454, USA. Tel: 781 7365 201; Fax: 781 7362 516; E-mail: bxu@brandeis.edu

Received 18 August 2016; Revised 28 November 2016; Accepted 30 November 2016

Edited by J Chipuk

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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.