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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.

SUBMITTER: Du X

PROVIDER: S-EPMC5386457 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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

Du Xuewen X Zhou Jie J Wang Huainin H Shi Junfeng J Kuang Yi Y Zeng Wu W Yang Zhimou Z Xu Bing B

Cell death & disease 20170216 2

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 nanofi ...[more]

PMID: 28206986

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Project description:The growing interest in gel-based additive manufacturing, also known as three-dimensional (3D) gel-printing technology, for research underscores the crucial need to develop robust biobased materials with excellent printing quality and reproducibility. The main focus of this study is to prepare and characterize some composite gels obtained with a low-molecular-weight gelling (LMWG) peptide called Fmoc-diphenylalanine (Fmoc-FF) and two types of cellulose nanofibrils (CNFs). The so-called Fmoc-FF peptide has the ability to self-assemble into a nanowire shape and therefore create an organized network that induces the formation of a gel. Despite their ease of preparation and potential use in biological systems, unfortunately, those Fmoc-FF nanowire gel systems cannot be 3D printed due to the high stiffness of the gel. For this reason, this study focuses on composite materials made of cellulose nanofibrils and Fmoc-FF nanowires, with the main objective being that the composite gels will be suitable for 3D printing applications. Two types of cellulose nanofibrils are employed in this study: (1) unmodified pristine cellulose nanofibrils (uCNF) and (2) chemically modified cellulose nanofibrils, which ones have been grafted with polymers containing the Fmoc unit on their backbone (CNF-g-Fmoc). The obtained products were characterized through solid-state cross-polarization magic angle-spinning 1H NMR and confocal laser scanning microscopy. Within these two CNF structures, two composite gels were produced: uCNF/Fmoc-FF and CNF-g-Fmoc/Fmoc-FF. The mechanical properties and printability of the composites are assessed using rheology and challenging 3D object printing. With the addition of water, different properties of the gels were observed. In this instance, CNF-g-Fmoc/Fmoc-FF (c = 5.1%) was selected as the most suitable option within this product range. For the composite bearing uCNF, exceptional print quality and mechanical properties are achieved with the CNF/Fmoc-FF gel (c = 5.1%). The structures are characterized by using field emission scanning electron microscopy (FESEM) and small-angle X-ray scattering (SAXS) measurements.

Dataset Information

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

Publications

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

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