title: In situ generated D-peptidic nanofibrils as multifaceted apoptotic inducers to target cancer cells.
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.
authors.affiliation: Department of Chemistry, Brandeis University, Waltham, MA 02454, USA.
authors.forename: Xuewen
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Chemistry, Brandeis University, Waltham, MA 02454, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Chemistry, Brandeis University, Waltham, MA 02454, USA.
authors.forename: Huainin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Brandeis University, Waltham, MA 02454, USA.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Chemistry, Brandeis University, Waltham, MA 02454, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Kuang
authors.affiliation: The Heller School for Social Policy and Management, Brandeis University, Waltham, MA 02454, USA.
authors.forename: Wu
authors.initials: W
authors.lastname: Zeng
authors.affiliation: The College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Zhimou
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Chemistry, Brandeis University, Waltham, MA 02454, USA.
authors.forename: Bing
authors.identifier: 0000-0002-4639-387X
authors.initials: B
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D006367:HeLa Cells; D006801:Humans; D057139:Nanofibers; D009369:Neoplasms / Q000276:immunology*; D010455:Peptides / Q000276:immunology* / Q000494:pharmacology
chemical_list: D010455:Peptides