A biomimetic platelet based on assembling peptides initiates artificial coagulation

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Abstract

A biomimetic platelet based on assembling peptides initiates artificial coagulation for tumor therapy.

Abstract

Platelets play a critical role in the regulation of coagulation, one of the essential processes in life, attracting great attention. However, mimicking platelets for in vivo artificial coagulation is still a great challenge due to the complexity of the process. Here, we design platelet-like nanoparticles (pNPs) based on self-assembled peptides that initiate coagulation and form clots in blood vessels. The pNPs first bind specifically to a membrane glycoprotein (i.e., CD105) overexpressed on angiogenetic endothelial cells in the tumor site and simultaneously transform into activated platelet-like nanofibers (apNFs) through ligand-receptor interactions. Next, the apNFs expose more binding sites and recruit and activate additional pNPs, forming artificial clots in both phantom and animal models. The pNPs are proven to be safe in mice without systemic coagulation. The self-assembling peptides mimic platelets and achieve artificial coagulation in vivo, thus providing a promising therapeutic strategy for tumors.

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Most cited references 33

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How to study proteins by circular dichroism.

Sharon Kelly, Thomas Jess, Nicholas C. Price (2005)

Circular dichroism (CD) is being increasingly recognised as a valuable technique for examining the structure of proteins in solution. However, the value of many studies using CD is compromised either by inappropriate experimental design or by lack of attention to key aspects of instrument calibration or sample characterisation. In this article, we summarise the basis of the CD approach and its application to the study of proteins, and then present clear guidelines on how reliable data can be obtained and analysed.

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Discovery and development of sorafenib: a multikinase inhibitor for treating cancer.

Scott Wilhelm, Christopher Carter, Mark Lynch … (2006)

Since the molecular revolution of the 1980s, knowledge of the aetiology of cancer has increased considerably, which has led to the discovery and development of targeted therapies tailored to inhibit cancer-specific pathways. The introduction and refinement of rapid, high-throughput screening technologies over the past decade has greatly facilitated this targeted discovery and development process. Here, we describe the discovery and continuing development of sorafenib (previously known as BAY 43-9006), the first oral multikinase inhibitor that targets Raf and affects tumour signalling and the tumour vasculature. The discovery cycle of sorafenib (Nexavar; Bayer Pharmaceuticals) - from initial screening for a lead compound to FDA approval for the treatment of advanced renal cell carcinoma in December 2005 - was completed in just 11 years, with approval being received approximately 5 years after the initiation of the first Phase I trial.

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Platelet biology and functions: new concepts and clinical perspectives

Paola van der Meijden, Johan Heemskerk (2018)

Platelets - blood cells continuously produced from megakaryocytes mainly in the bone marrow - are implicated not only in haemostasis and arterial thrombosis, but also in other physiological and pathophysiological processes. This Review describes current evidence for the heterogeneity in platelet structure, age, and activation properties, with consequences for a diversity of platelet functions. Signalling processes of platelet populations involved in thrombus formation with ongoing coagulation are well understood. Genetic approaches have provided information on multiple genes related to normal haemostasis, such as those encoding receptors and signalling or secretory proteins, that determine platelet count and/or responsiveness. As highly responsive and secretory cells, platelets can alter the environment through the release of growth factors, chemokines, coagulant factors, RNA species, and extracellular vesicles. Conversely, platelets will also adapt to their environment. In disease states, platelets can be positively primed to reach a pre-activated condition. At the inflamed vessel wall, platelets interact with leukocytes and the coagulation system, interactions mediating thromboinflammation. With current antiplatelet therapies invariably causing bleeding as an undesired adverse effect, novel therapies can be more beneficial if directed against specific platelet responses, populations, interactions, or priming conditions. On the basis of these novel concepts and processes, we discuss several initiatives to target platelets therapeutically.

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Author and article information

Journal

Journal ID (nlm-ta): Sci Adv

Journal ID (iso-abbrev): Sci Adv

Journal ID (publisher-id): SciAdv

Journal ID (hwp): advances

Title: Science Advances

Publisher: American Association for the Advancement of Science

ISSN (Electronic): 2375-2548

Publication date Collection: May 2020

Publication date (Electronic): 27 May 2020

Volume: 6

Issue: 22

Electronic Location Identifier: eaaz4107

Affiliations

[1 ]CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun, Beijing 100190, P. R. China.

[2 ]Faculty of Chemistry, Northeast Normal University, Changchun 130024, P. R. China.

[3 ]Key Laboratory of Functional Small Organic Molecule, College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang 330022, P. R. China.

[4 ]State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Functional Polymer Materials of Ministry of Education College of Chemistry, Nankai University, Tianjin 300071, P. R. China.

[5 ]Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, P. R. China.

[6 ]Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, P. R. China.

Author notes

[*]

These authors contributed equally to this work.

[† ]Corresponding author. Email: wanghao@ 123456nanoctr.cn (H.W.); wanglei@ 123456nanoctr.cn (L.W.)

Author information

Pei-Pei Yang http://orcid.org/0000-0002-3896-0758

Kuo Zhang http://orcid.org/0000-0003-3687-3172

Ping-Ping He http://orcid.org/0000-0002-6557-0982

Yu Fan http://orcid.org/0000-0001-8917-7600

Xingfa Gao http://orcid.org/0000-0002-0643-9319

Zi-Ming Chen http://orcid.org/0000-0002-1704-0602

Da-Yong Hou http://orcid.org/0000-0002-7567-8663

Yuan Li http://orcid.org/0000-0002-4588-8977

Yu Yi http://orcid.org/0000-0003-3272-5092

Dong-Bing Cheng http://orcid.org/0000-0002-1413-7601

Jing-Ping Zhang http://orcid.org/0000-0001-8004-3673

Linqi Shi http://orcid.org/0000-0002-9534-795X

Xian-Zheng Zhang http://orcid.org/0000-0001-6242-6005

Lei Wang http://orcid.org/0000-0003-1405-9815

Hao Wang http://orcid.org/0000-0002-1961-0787

Article

Publisher ID: aaz4107

DOI: 10.1126/sciadv.aaz4107

PMC ID: 7385434

SO-VID: 614e93a4-9280-4563-a3b2-60c92beaf714

Copyright © Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

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This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

History

Date received : 09 September 2019

Date accepted : 18 March 2020

Funding

Funded by: doi http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Funded by: CAS Key Research Program for Frontier Sciences;

Funded by: Key Project of the Chinese Academy of Sciences in Cooperation with Foreign Enterprises;

Funded by: Jilin Province Key Laboratory of Organic Functional Molecular Design and Synthesis;

A biomimetic platelet based on assembling peptides initiates artificial coagulation

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Artificial Intelligence in Medicine

Most cited references 33

How to study proteins by circular dichroism.

Discovery and development of sorafenib: a multikinase inhibitor for treating cancer.

Platelet biology and functions: new concepts and clinical perspectives

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