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      Her2-Functionalized Gold-Nanoshelled Magnetic Hybrid Nanoparticles: a Theranostic Agent for Dual-Modal Imaging and Photothermal Therapy of Breast Cancer

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          Abstract

          Targeted theranostic platform that integrates multi-modal imaging and therapeutic function is emerging as a promising strategy for earlier detection and precise treatment of cancer. Herein, we designed targeted gold-nanoshelled poly (lactic-co-glycolic acid) (PLGA) magnetic hybrid nanoparticles carrying anti-human epidermal growth factor receptor 2 (Her2) antibodies (Her2-GPH NPs) for dual-modal ultrasound (US)/magnetic resonance (MR) imaging and photothermal therapy of breast cancer. The agent was fabricated by coating gold nanoshell around PLGA nanoparticles co-loaded with perfluorooctyl bromide (PFOB) and superparamagnetic iron oxide nanoparticles (SPIOs), followed by conjugating with anti-Her2 antibodies. Cell-targeting studies demonstrated receptor-mediated specific binding of the agent to Her2-positive human breast cancer SKBR3 cells, and its binding rate was significantly higher than that of Her2-negative cells ( P < 0.001). In vitro, the agent had capabilities for contrast-enhanced US imaging as well as T 2-weighted MR imaging with a relatively high relaxivity ( r 2 = 441.47 mM −1 s −1). Furthermore, the Her2 functionalization of the agent prominently enhanced the US/MR molecular imaging effect of targeted cells by cell-specific binding. Live/dead cell assay and targeted photothermal cytotoxicity experiments confirmed that Her2-GPH NPs could serve as effective photoabsorbers to specifically induce SKBR3 cell death upon near-infrared laser irradiation. In summary, Her2-GPH NPs were demonstrated to be novel targeted theranostic agents with great potential to facilitate early non-invasive diagnosis and adjuvant therapy of breast cancer.

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          The online version of this article (10.1186/s11671-019-3053-4) contains supplementary material, which is available to authorized users.

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          Imaging and drug delivery using theranostic nanoparticles.

          Nanoparticle technologies are significantly impacting the development of both therapeutic and diagnostic agents. At the intersection between treatment and diagnosis, interest has grown in combining both paradigms into clinically effective formulations. This concept, recently coined as theranostics, is highly relevant to agents that target molecular biomarkers of disease and is expected to contribute to personalized medicine. Here we review state-of-the-art nanoparticles from a therapeutic and a diagnostic perspective and discuss challenges in bringing these fields together. Major classes of nanoparticles include, drug conjugates and complexes, dendrimers, vesicles, micelles, core-shell particles, microbubbles, and carbon nanotubes. Most of these formulations have been described as carriers of either drugs or contrast agents. To observe these formulations and their interactions with disease, a variety of contrast agents have been used, including optically active small molecules, metals and metal oxides, ultrasonic contrast agents, and radionuclides. The opportunity to rapidly assess and adjust treatment to the needs of the individual offers potential advantages that will spur the development of theranostic agents. Copyright © 2010 Elsevier B.V. All rights reserved.
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            Current advances in research and clinical applications of PLGA-based nanotechnology.

            Co-polymer poly(lactic-co-glycolic acid) (PLGA) nanotechnology has been developed for many years and has been approved by the US FDA for the use of drug delivery, diagnostics and other applications of clinical and basic science research, including cardiovascular disease, cancer, vaccine and tissue engineering. This article presents the more recent successes of applying PLGA-based nanotechnologies and tools in these medicine-related applications. It focuses on the possible mechanisms, diagnosis and treatment effects of PLGA preparations and devices. This updated information will benefit to both new and established research scientists and clinical physicians who are interested in the development and application of PLGA nanotechnology as new therapeutic and diagnostic strategies for many diseases.
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              Theranostic magnetic nanoparticles.

              Early detection and treatment of disease is the most important component of a favorable prognosis. Biomedical researchers have thus invested tremendous effort in improving imaging techniques and treatment methods. Over the past decade, concepts and tools derived from nanotechnology have been applied to overcome the problems of conventional techniques for advanced diagnosis and therapy. In particular, advances in nanoparticle technology have created new paradigms for theranostics, which is defined as the combination of therapeutic and diagnostic agents within a single platform. In this Account, we examine the potential advantages and opportunities afforded by magnetic nanoparticles as platform materials for theranostics. We begin with a brief overview of relevant magnetic parameters, such as saturation magnetization, coercivity, and magnetocrystalline anisotropy. Understanding the interplay of these parameters is critical for optimizing magnetic characteristics needed for effective imaging and therapeutics, which include magnetic resonance imaging (MRI) relaxivity, heat emission, and attractive forces. We then discuss approaches to constructing an MRI nanoparticle contrast agent with high sensitivity. We further introduce a new design concept for a fault-free contrast agent, which is a T1 and T2 dual mode hybrid. Important capabilities of magnetic nanoparticles are the external controllability of magnetic heat generation and magnetic attractive forces for the transportation and movement of biological objects. We show that these functions can be utilized not only for therapeutic hyperthermia of cancer but also for controlled release of cancer drugs through the application of an external magnetic field. Additionally, the use of magnetic nanoparticles to drive mechanical forces is demonstrated to be useful for molecular-level cell signaling and for controlling the ultimate fate of the cell. Finally, we show that targeted imaging and therapy are made possible by attaching a variety of imaging and therapeutic components. These added components include therapeutic genes (small interfering RNA, or siRNA), cancer-specific ligands, and optical reporting dyes. The wide range of accessible features of magnetic nanoparticles underscores their potential as the most promising platform material available for theranostics.
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                Author and article information

                Contributors
                dongqi6161@163.com
                yanghong@shnu.edu.cn
                wancaifengky@sina.com
                zhengdongdongcool@163.com
                zgzhou@shnu.edu.cn
                shaoweixie@yeah.net
                ly230502@163.com
                +86-21-68383371 , beautydujing@163.com
                fenghua-li@163.com
                Journal
                Nanoscale Res Lett
                Nanoscale Res Lett
                Nanoscale Research Letters
                Springer US (New York )
                1931-7573
                1556-276X
                26 August 2019
                26 August 2019
                2019
                : 14
                : 235
                Affiliations
                [1 ]ISNI 0000 0004 0368 8293, GRID grid.16821.3c, Department of Ultrasound, Renji Hospital, School of Medicine, , Shanghai Jiao Tong University, ; Shanghai, 200127 China
                [2 ]ISNI 0000 0001 0701 1077, GRID grid.412531.0, Department of Chemistry, College of Life and Environmental Science, , Shanghai Normal University, ; Shanghai, 200234 China
                Author information
                http://orcid.org/0000-0002-3726-5059
                Article
                3053
                10.1186/s11671-019-3053-4
                6709082
                31448377
                d39ebe1e-7e79-421c-a8a5-3fd54c02312e
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 28 March 2019
                : 17 June 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81571678
                Award ID: 81801697
                Award Recipient :
                Funded by: Scientific Research and Cultivating Foundation of Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine
                Award ID: RJZZ17-015
                Award Recipient :
                Funded by: Scientific Research Plan Project of Shanghai Science and Technology Commission
                Award ID: 16411968800
                Award Recipient :
                Categories
                Nano Express
                Custom metadata
                © The Author(s) 2019

                Nanomaterials
                theranostic agent,anti-her2 antibody,ultrasound imaging,magnetic resonance imaging,photothermal therapy,breast cancer

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