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      Integrin α vβ 3-targeted polydopamine-coated gold nanostars for photothermal ablation therapy of hepatocellular carcinoma

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          Abstract

          Photothermal therapy (PTT) has emerged as a promising cancer therapeutic method. In this study, Arg-Gly-Asp (RGD) peptide-conjugated polydopamine-coated gold nanostars (Au@PDA-RGD NPs) were prepared for targeting PTT of hepatocellular carcinoma (HCC). A polydopamine (PDA) shell was coated on the surface of gold nanostars by the oxidative self-polymerization of dopamine (termed as Au@PDA NPs). Au@PDA NPs were further functionalized with polyethylene glycol and RGD peptide to improve biocompatibility as well as selectivity toward the HCC cells. Au@PDA-RGD NPs showed an intense absorption at 822 nm, which makes them suitable for near-infrared-excited PTT. Our results indicated that the Au@PDA-RGD NPs were effective for the PTT therapy of the α Vβ 3 integrin receptor-overexpressed HepG2 cells in vitro. Further antitumor mechanism studies showed that the Au@PDA-RGD NPs-based PTT induced human liver cancer cells death via the mitochondrial–lysosomal and autophagy pathways. In vivo experiments showed that Au@PDA-RGD NPs had excellent tumor treatment efficiency and negligible side effects. Thus, our study showed that Au@PDA-RGD NPs could offer an excellent nanoplatform for PTT of HCC.

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          Most cited references52

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          Versatile Polydopamine Platforms: Synthesis and Promising Applications for Surface Modification and Advanced Nanomedicine

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            Gold nanostars: surfactant-free synthesis, 3D modelling, and two-photon photoluminescence imaging.

            Understanding the control of the optical and plasmonic properties of unique nanosystems--gold nanostars--both experimentally and theoretically permits superior design and fabrication for biomedical applications. Here, we present a new, surfactant-free synthesis method of biocompatible gold nanostars with adjustable geometry such that the plasmon band can be tuned into the near-infrared region 'tissue diagnostic window', which is most suitable for in vivo imaging. Theoretical modelling was performed for multiple-branched 3D nanostars and yielded absorption spectra in good agreement with experimental results. The plasmon band shift was attributed to variations in branch aspect ratio, and the plasmon band intensifies with increasing branch number, branch length, and overall star size. Nanostars showed an extremely strong two-photon photoluminescence (TPL) process. The TPL imaging of wheat-germ agglutinin (WGA) functionalized nanostars on BT549 breast cancer cells and of PEGylated nanostars circulating in the vasculature, examined through a dorsal window chamber in vivo in laboratory mouse studies, demonstrated that gold nanostars can serve as an efficient contrast agent for biological imaging applications.
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              Mussel-inspired polydopamine: a biocompatible and ultrastable coating for nanoparticles in vivo.

              Bioinspired polydopamine (PDA) has served as a universal coating to nanoparticles (NPs) for various biomedical applications. However, one remaining critical question is whether the PDA shell on NPs is stable in vivo. In this study, we modified gold nanoparticles (GNPs) with finely controlled PDA nanolayers to form uniform core/shell nanostructures (GNP@PDA). In vitro study showed that the PDA-coated GNPs had low cytotoxicity and could smoothly translocate to cancer cells. Transmission electron microscopy (TEM) analysis demonstrated that the PDA nanoshells were intact within cells after 24 h incubation. Notably, we found the GNP@PDA could partially escape from the endosomes/lysosomes to cytosol and locate close to the nucleus. Furthermore, we observed that the PDA-coated NPs have very different uptake behavior in two important organs of the liver and spleen: GNP@PDA in the liver were mainly uptaken by the Kupffer cells, while the GNP@PDA in the spleen were uptaken by a variety of cells. Importantly, we proved the PDA nanoshells were stable within cells of the liver and spleen for at least six weeks, and GNP@PDA did not show notable histological toxicity to main organs of mice in a long time. These results provided the direct evidence to support that the PDA surface modification can serve as an effective strategy to form ultrastable coatings on NPs in vivo, which can improve the intracellular delivery capacity and biocompatibility of NPs for biomedical application.
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                Author and article information

                Journal
                Regen Biomater
                Regen Biomater
                rb
                Regenerative Biomaterials
                Oxford University Press
                2056-3418
                2056-3426
                October 2021
                10 August 2021
                10 August 2021
                : 8
                : 5
                : rbab046
                Affiliations
                [1 ]Zhong Yuan Academy of Biological Medicine, Liaocheng People’s Hospital , No. 67 Dongchang West Road, Liaocheng 252000, China
                [2 ]Clinical Laboratory, Liaocheng People’s Hospital , No. 67 Dongchang West Road, Liaocheng 252000, China
                [3 ]Department of Hepatobiliary Surgery, Liaocheng People’s Hospital , No. 67 Dongchang West Road, Liaocheng 252000, China
                [4 ]Liaocheng People’s Hospital, Medical College of Liaocheng University , No. 67 Dongchang West Road, Liaocheng 252000, China
                [5 ]School of Basic Medical Sciences, Shandong University , No.44 Wenhua West Road, Jinan 250012, China
                Author notes
                Correspondence address. Zhong Yuan Academy of Biological Medicine, Liaocheng People's Hospital, No. 67 Dongchang west Road, Liaocheng 252000, China. Tel/Fax: +86-635-827-0102; E-mail: xhjiang_sd@ 123456163.com
                Author information
                https://orcid.org/0000-0002-1192-8002
                https://orcid.org/0000-0003-2390-0952
                Article
                rbab046
                10.1093/rb/rbab046
                8387661
                34457350
                b1684db0-8032-4cde-9946-4dd447b2c00b
                © The Author(s) 2021. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 September 2020
                : 13 July 2021
                : 30 July 2021
                : 23 August 2021
                Page count
                Pages: 14
                Funding
                Funded by: National Natural Science Foundation of China, DOI 10.13039/501100001809;
                Award ID: NSFC81602736
                Funded by: China Postdoctoral Science Foundation, DOI 10.13039/501100002858;
                Award ID: 2018M632684
                Funded by: Shandong Provincial Natural Science Foundation, DOI 10.13039/501100007129;
                Award ID: ZR2019PH084
                Funded by: Liaocheng People's Hospital Youth Research Fund;
                Award ID: LYQN201935
                Categories
                Research Article
                AcademicSubjects/MED00010
                AcademicSubjects/SCI01410

                polydopamine-coated gold nanostars,rgd peptide,targeted photothermal therapy,hepatocellular carcinoma

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