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      Fe 3O 4-Au Core-Shell Nanoparticles as a Multimodal Platform for In Vivo Imaging and Focused Photothermal Therapy

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          Abstract

          In this study, we report the synthesis of gold-coated iron oxide nanoparticles capped with polyvinylpyrrolidone (Fe@Au NPs). The as-synthesized nanoparticles (NPs) exhibited good stability in aqueous media and excellent features as contrast agents (CA) for both magnetic resonance imaging (MRI) and X-ray computed tomography (CT). Additionally, due to the presence of the local surface plasmon resonances of gold, the NPs showed exploitable “light-to-heat” conversion ability in the near-infrared (NIR) region, a key attribute for effective photothermal therapies (PTT). In vitro experiments revealed biocompatibility as well as excellent efficiency in killing glioblastoma cells via PTT. The in vivo nontoxicity of the NPs was demonstrated using zebrafish embryos as an intermediate step between cells and rodent models. To warrant that an effective therapeutic dose was achieved inside the tumor, both intratumoral and intravenous routes were screened in rodent models by MRI and CT. The pharmacokinetics and biodistribution confirmed the multimodal imaging CA capabilities of the Fe@AuNPs and revealed constraints of the intravenous route for tumor targeting, dictating intratumoral administration for therapeutic applications. Finally, Fe@Au NPs were successfully used for an in vivo proof of concept of imaging-guided focused PTT against glioblastoma multiforme in a mouse model.

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          Combination therapy in combating cancer

          Combination therapy, a treatment modality that combines two or more therapeutic agents, is a cornerstone of cancer therapy. The amalgamation of anti-cancer drugs enhances efficacy compared to the mono-therapy approach because it targets key pathways in a characteristically synergistic or an additive manner. This approach potentially reduces drug resistance, while simultaneously providing therapeutic anti-cancer benefits, such as reducing tumour growth and metastatic potential, arresting mitotically active cells, reducing cancer stem cell populations, and inducing apoptosis. The 5-year survival rates for most metastatic cancers are still quite low, and the process of developing a new anti-cancer drug is costly and extremely time-consuming. Therefore, new strategies that target the survival pathways that provide efficient and effective results at an affordable cost are being considered. One such approach incorporates repurposing therapeutic agents initially used for the treatment of different diseases other than cancer. This approach is effective primarily when the FDA-approved agent targets similar pathways found in cancer. Because one of the drugs used in combination therapy is already FDA-approved, overall costs of combination therapy research are reduced. This increases cost efficiency of therapy, thereby benefiting the “medically underserved”. In addition, an approach that combines repurposed pharmaceutical agents with other therapeutics has shown promising results in mitigating tumour burden. In this systematic review, we discuss important pathways commonly targeted in cancer therapy. Furthermore, we also review important repurposed or primary anti-cancer agents that have gained popularity in clinical trials and research since 2012.
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            Phosphorylation of EZH2 activates STAT3 signaling via STAT3 methylation and promotes tumorigenicity of glioblastoma stem-like cells.

            Glioblastoma multiforme (GBM) displays cellular hierarchies harboring a subpopulation of stem-like cells (GSCs). Enhancer of Zeste Homolog 2 (EZH2), the lysine methyltransferase of Polycomb repressive complex 2, mediates transcriptional repression of prodifferentiation genes in both normal and neoplastic stem cells. An oncogenic role of EZH2 as a transcriptional silencer is well established; however, additional functions of EZH2 are incompletely understood. Here, we show that EZH2 binds to and methylates STAT3, leading to enhanced STAT3 activity by increased tyrosine phosphorylation of STAT3. The EZH2-STAT3 interaction preferentially occurs in GSCs relative to non-stem bulk tumor cells, and it requires a specific phosphorylation of EZH2. Inhibition of EZH2 reverses the silencing of Polycomb target genes and diminishes STAT3 activity, suggesting therapeutic strategies. Copyright © 2013 Elsevier Inc. All rights reserved.
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              Microscale Heat Transfer Transduced by Surface Plasmon Resonant Gold Nanoparticles.

              Visible radiation at resonant frequencies is transduced to thermal energy by surface plasmons on gold nanoparticles. Temperature in
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                20 March 2021
                March 2021
                : 13
                : 3
                : 416
                Affiliations
                [1 ]BIONAND—Centro Andaluz de Nanomedicina y Biotecnología (Junta de Andalucía-Universidad de Málaga), C/Severo Ochoa, 35, 29590 Málaga, Spain; ccaro@ 123456bionand.es (C.C.); jpaez@ 123456bionand.es (J.M.P.-M.); adominguez@ 123456bionand.es (A.D.); jrpearson@ 123456bionand.es (J.R.P.)
                [2 ]Departamento de Química Física, Universidad de Granada, Avenida de la Fuente Nueva S/N, 18071 Granada, Spain; fgammar@ 123456gmail.com
                [3 ]REQUIMTE/LAQV, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto, 4169-007 Porto, Portugal; pedro.cq1@ 123456gmail.com
                [4 ]Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, 41012 Seville, Spain; mpernia@ 123456us.es
                [5 ]Departamento de Ingeniería y Ciencia de los Materiales y del Transporte, Escuela Politécnica Superior, Universidad de Sevilla, Virgen de África 7, 41011 Sevilla, Spain; abeltran3@ 123456us.es
                [6 ]Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, 50009 Zaragoza, Spain; yfdezafonso@ 123456gmail.com (Y.F.-A.); jmfuente@ 123456unizar.es (J.M.D.l.F.)
                [7 ]Biomedical Research Networking Center in Bioengineering, Biomaterials &Nanomedicine (CIBER-BBN), 28029 Madrid, Spain
                [8 ]UCIBIO, REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal; rft@ 123456fct.unl.pt
                Author notes
                [* ]Correspondence: efpereir@ 123456fc.up.pt (E.P.); mlgarcia@ 123456bionand.es (M.L.G.-M.)
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0003-4758-3816
                https://orcid.org/0000-0001-6937-9950
                https://orcid.org/0000-0001-7032-7760
                https://orcid.org/0000-0002-1419-0058
                https://orcid.org/0000-0002-2267-0844
                https://orcid.org/0000-0001-8160-0574
                https://orcid.org/0000-0003-2599-5908
                https://orcid.org/0000-0002-0970-1917
                https://orcid.org/0000-0003-1081-8482
                https://orcid.org/0000-0002-5139-2871
                https://orcid.org/0000-0003-2086-5696
                https://orcid.org/0000-0002-2257-7682
                Article
                pharmaceutics-13-00416
                10.3390/pharmaceutics13030416
                8003746
                33804636
                c77aec10-c44b-4772-98d7-541a21e988c1
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 17 February 2021
                : 12 March 2021
                Categories
                Article

                imaging-guided therapy,multimodal imaging,contrast agent,mri,ct

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