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      Delivery of Phosphorescent Anticancer Iridium(III) Complexes by Polydopamine Nanoparticles for Targeted Combined Photothermal‐Chemotherapy and Thermal/Photoacoustic/Lifetime Imaging

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          Abstract

          Recently, phosphorescent iridium complexes have demonstrated great potential as anticancer and imaging agents. Dopamine is a melanin‐like mimic of mussel adhesive protein that can self‐polymerize to form polydopamine (PDA) nanoparticles that demonstrate favorable biocompatibility, near‐infrared absorption, and photothermal effects. Herein, PDA nanoparticles are functionalized with β‐cyclodextrin (CD) substitutions, which are further assembled with adamantane‐modified arginine‐glycine‐aspartic acid (Ad‐RGD) tripeptides to target integrin‐rich tumor cells. The thus formed PDA‐CD‐RGD nanoparticles can deliver a phosphorescent iridium(III) complexes LysoIr ([Ir(ppy) 2( l)]PF 6, ppy = 2‐phenylpyridine, L = (1‐(2‐quinolinyl)‐β‐carboline) to form a theranostic platform LysoIr@PDA‐CD‐RGD. It is demonstrated that LysoIr@PDA‐CD‐RGD can be applied for targeted combined cancer photothermal‐chemotherapy and thermal/photoacoustic/two‐photon phosphorescence lifetime imaging under both in vitro and in vivo conditions. This work provides a useful strategy to construct multifunctional nanocomposites for the optimization of metal‐based anticancer agents for further biomedical applications.

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          Control of apoptosis by the cellular ATP level.

          Apoptosis is a physiological form of cell death. Its causes and execution mechanisms are not clearly understood. Oxidative stress, nitric oxide and its congeners, Ca2+, proteases, nucleases, and mitochondria are considered mediators of apoptosis. At present their importance and exact role are elusive but it is clear that mitochondria are both the target and the source of oxidative stress, nitric oxide, and Ca2+. The mitochondrial membrane potential (delta psi), which is the driving force for mitochondrial ATP synthesis, declines during apoptosis, and maintenance of delta psi prevents apoptosis. Since apoptosis is highly regulated and involves the activity of hydrolytic enzymes, chromatin condensation and vesicle formation apoptosis is likely to have a high energy demand. We propose that the cellular ATP level is an important determinant for cell death. This hypothesis is supported by circumstantial evidence, is consistent with the available data, has a corrolary in aging, and is amenable to direct experimental testing particularly with flow cytometry as a promising tool.
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            A Multifunctional Platform for Tumor Angiogenesis-Targeted Chemo-Thermal Therapy Using Polydopamine-Coated Gold Nanorods.

            Image-guided combined chemo-thermal therapy assists in optimizing treatment time, enhancing therapeutic efficiency, and circumventing side effects. In the present study, we developed a chemo-photothermal theranostic platform based on polydopamine (PDA)-coated gold nanorods (GNRs). The PDA coating was thin; however, it significantly suppressed the cytotoxicity of the cetyltrimethylammonium bromide template and allowed high cisplatin loading efficiency, arginine-glycine-aspartic acid (RGD) peptide (c(RGDyC)) conjugation, and chelator-free iodine-125 labeling (RGD-125IPt-PDA@GNRs). While loaded cisplatin was released in a pH-sensitive manner, labeled125I was outstandingly stable under biological conditions. RGD-125IPt-PDA@GNRs had a high specificity for αvβ3integrin, and consequently, they could selectively accumulate in tumors, as revealed by single photon emission computed tomography/CT imaging, and in target tumor angiogenic vessels, as shown by high-resolution photoacoustic imaging. As RGD-125IPt-PDA@GNRs targets tumor angiogenesis, it is a highly potent tumor therapy. Combined chemo-photothermal therapy with probes could thoroughly ablate tumors and inhibit tumor relapse via a synergistic antitumor effect. Our studies demonstrated that RGD-125IPt-PDA@GNRs is a robust platform for image-guided, chemo-thermal tumor therapy with outstanding synergistic tumor killing and relapse inhibition effects.
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              Graphene Oxide Decorated with Ru(II)–Polyethylene Glycol Complex for Lysosome-Targeted Imaging and Photodynamic/Photothermal Therapy

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                Author and article information

                Contributors
                tancaip@mail.sysu.edu.cn
                cesmzw@mail.sysu.edu.cn
                Journal
                Adv Sci (Weinh)
                Adv Sci (Weinh)
                10.1002/(ISSN)2198-3844
                ADVS
                Advanced Science
                John Wiley and Sons Inc. (Hoboken )
                2198-3844
                15 August 2018
                October 2018
                : 5
                : 10 ( doiID: 10.1002/advs.v5.10 )
                : 1800581
                Affiliations
                [ 1 ] MOE Key Laboratory of Bioinorganic and Synthetic Chemistry School of Chemistry Sun Yat‐Sen University Guangzhou 510275 P. R. China
                Author notes
                Author information
                http://orcid.org/0000-0001-7131-1154
                Article
                ADVS766
                10.1002/advs.201800581
                6193176
                30356964
                de3e4fc4-866a-46a2-b7c3-9796a772b06e
                © 2018 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 April 2018
                : 28 June 2018
                Page count
                Figures: 10, Tables: 0, Pages: 12, Words: 6030
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 21778078
                Award ID: 21571196
                Award ID: 21572282
                Award ID: 2187100x
                Funded by: 973 program
                Award ID: 2014CB845604
                Award ID: 2015CB856301
                Funded by: Ministry of Education of China
                Award ID: IRT‐17R111
                Funded by: Guangdong Natural Science Foundation
                Award ID: 2015A030306023
                Funded by: Fundamental Research Funds for the Central Universities
                Categories
                Full Paper
                Full Papers
                Custom metadata
                2.0
                advs766
                October 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.5.0.1 mode:remove_FC converted:18.10.2018

                combined therapy,iridium complexes,polydopamine,thermal/photoacoustic/lifetime imaging

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