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      Insights into the angiogenic effects of nanomaterials: mechanisms involved and potential applications

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          Abstract

          The vascular system, which transports oxygen and nutrients, plays an important role in wound healing, cardiovascular disease treatment and bone tissue engineering. Angiogenesis is a complex and delicate regulatory process. Vascular cells, the extracellular matrix (ECM) and angiogenic factors are indispensable in the promotion of lumen formation and vascular maturation to support blood flow. However, the addition of growth factors or proteins involved in proangiogenic effects is not effective for regulating angiogenesis in different microenvironments. The construction of biomaterial scaffolds to achieve optimal growth conditions and earlier vascularization is undoubtedly one of the most important considerations and major challenges among engineering strategies. Nanomaterials have attracted much attention in biomedical applications due to their structure and unique photoelectric and catalytic properties. Nanomaterials not only serve as carriers that effectively deliver factors such as angiogenesis-related proteins and mRNA but also simulate the nano-topological structure of the primary ECM of blood vessels and stimulate the gene expression of angiogenic effects facilitating angiogenesis. Therefore, the introduction of nanomaterials to promote angiogenesis is a great helpful to the success of tissue regeneration and some ischaemic diseases. This review focuses on the angiogenic effects of nanoscaffolds in different types of tissue regeneration and discusses the influencing factors as well as possible related mechanisms of nanomaterials in endothelial neovascularization. It contributes novel insights into the design and development of novel nanomaterials for vascularization and therapeutic applications.

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          Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts.

          Nanoparticles in a biological fluid (plasma, or otherwise) associate with a range of biopolymers, especially proteins, organized into the "protein corona" that is associated with the nanoparticle and continuously exchanging with the proteins in the environment. Methodologies to determine the corona and to understand its dependence on nanomaterial properties are likely to become important in bionanoscience. Here, we study the long-lived ("hard") protein corona formed from human plasma for a range of nanoparticles that differ in surface properties and size. Six different polystyrene nanoparticles were studied: three different surface chemistries (plain PS, carboxyl-modified, and amine-modified) and two sizes of each (50 and 100 nm), enabling us to perform systematic studies of the effect of surface properties and size on the detailed protein coronas. Proteins in the corona that are conserved and unique across the nanoparticle types were identified and classified according to the protein functional properties. Remarkably, both size and surface properties were found to play a very significant role in determining the nanoparticle coronas on the different particles of identical materials. We comment on the future need for scientific understanding, characterization, and possibly some additional emphasis on standards for the surfaces of nanoparticles.
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            Fatty acid carbon is essential for dNTP synthesis in endothelial cells

            The metabolism of endothelial cells (ECs) during vessel sprouting remains poorly studied. Here, we report that endothelial loss of CPT1a, a rate-limiting enzyme of fatty acid oxidation (FAO), caused vascular sprouting defects due to impaired proliferation, not migration of ECs. Reduction of FAO in ECs did not cause energy depletion or disturb redox homeostasis, but impaired de novo nucleotide synthesis for DNA replication. Isotope labeling studies in control ECs showed that fatty acid carbons substantially replenished the Krebs cycle, and were incorporated into aspartate (a nucleotide precursor), uridine monophosphate (a precursor of pyrimidine nucleoside triphosphates) and DNA. CPT1a silencing reduced these processes and depleted EC stores of aspartate and deoxyribonucleoside triphosphates. Acetate (metabolized to acetyl-CoA, thereby substituting for the depleted FAO-derived acetyl-CoA) or a nucleoside mix rescued the phenotype of CPT1a-silenced ECs. Finally, CPT1 blockade inhibited pathological ocular angiogenesis, suggesting a novel strategy for blocking angiogenesis.
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              Endothelial-mural cell signaling in vascular development and angiogenesis.

              Mural cells are essential components of blood vessels and are necessary for normal development, homeostasis, and organ function. Alterations in mural cell density or the stable attachment of mural cells to the endothelium is associated with several human diseases such as diabetic retinopathy, venous malformation, and hereditary stroke. In addition mural cells are implicated in regulating tumor growth and have thus been suggested as potential antiangiogenic targets in tumor therapy. In recent years our knowledge of mural cell function and endothelial-mural cell signaling has increased dramatically, and we now begin to understand the mechanistic basis of the key signaling pathways involved. This is mainly thanks to sophisticated in vivo experiments using a broad repertoire of genetic technologies. In this review, we summarize the five currently best understood signaling pathways implicated in mural cell biology. We discuss PDGFB/PDGFRbeta- dependent pericyte recruitment, as well as the role of angiopoietins and Tie receptors in vascular maturation. In addition, we highlight the effects of sphingosine-1-phosphate signaling on adherens junction assembly and vascular stability, as well as the role of TGF-beta-signaling in mural cell differentiation. We further reflect recent data suggesting an important function for Notch3 signaling in mural cell maturation.
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                Author and article information

                Contributors
                shaolongquan@smu.edu.cn
                Journal
                J Nanobiotechnology
                J Nanobiotechnology
                Journal of Nanobiotechnology
                BioMed Central (London )
                1477-3155
                9 January 2020
                9 January 2020
                2020
                : 18
                : 9
                Affiliations
                [1 ]ISNI 0000 0000 8877 7471, GRID grid.284723.8, Stomatological Hospital, , Southern Medical University, ; Guangzhou, 510280 China
                [2 ]GRID grid.484195.5, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, ; Guangzhou, 510515 China
                Article
                570
                10.1186/s12951-019-0570-3
                6950937
                31918719
                e43433cb-0d5d-4d6b-84e2-cbf50f7ed64f
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 28 October 2019
                : 31 December 2019
                Funding
                Funded by: National Key Research and Development Program of China
                Award ID: 2016YFC1102605
                Award ID: 2016YFC1102603
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81870786
                Award Recipient :
                Funded by: Medical Scientific Research Foundation of Guangdong Province
                Award ID: B2018119
                Award Recipient :
                Funded by: Science Foundation of Southern Medical University
                Award ID: PY2018N093
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2020

                Biotechnology
                nanomaterials,blood vessel,endothelial cells,angiogenesis,tissue regeneration,angiogenic property

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