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      Magnetic Enrichment of Dendritic Cell Vaccine in Lymph Node with Fluorescent-Magnetic Nanoparticles Enhanced Cancer Immunotherapy

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          Abstract

          Dendritic cell (DC) migration to the lymph node is a key component of DC-based immunotherapy. However, the DC homing rate to the lymphoid tissues is poor, thus hindering the DC-mediated activation of antigen-specific T cells. Here, we developed a system using fluorescent magnetic nanoparticles (α-AP-fmNPs; loaded with antigen peptide, iron oxide nanoparticles, and indocyanine green) in combination with magnetic pull force (MPF) to successfully manipulate DC migration in vitro and in vivo. α-AP-fmNPs endowed DCs with MPF-responsiveness, antigen presentation, and simultaneous optical and magnetic resonance imaging detectability. We showed for the first time that α-AP-fmNP-loaded DCs were sensitive to MPF, and their migration efficiency could be dramatically improved both in vitro and in vivo through MPF treatment. Due to the enhanced migration of DCs, MPF treatment significantly augmented antitumor efficacy of the nanoparticle-loaded DCs. Therefore, we have developed a biocompatible approach with which to improve the homing efficiency of DCs and subsequent anti-tumor efficacy, and track their migration by multi-modality imaging, with great potential applications for DC-based cancer immunotherapy.

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          Most cited references36

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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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            Strategies for the intracellular delivery of nanoparticles.

            The ability to target contrast agents and therapeutics inside cells is becoming important as we strive to decipher the complex network of events that occur within living cells and design therapies that can modulate these processes. Nanotechnology researchers have generated a growing list of nanoparticles designed for such applications. These particles can be assembled from a variety of materials into desirable geometries and configurations and possess useful properties and functionalities. Undoubtedly, the effective delivery of these nanomaterials into cells will be critical to their applications. In this tutorial review, we discuss the fundamental challenges of delivering nanoparticles into cells and to the targeted organelles, and summarize strategies that have been developed to-date.
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              Regulation of Dendritic Cell Migration to the Draining Lymph Node

              Antigen-pulsed dendritic cells (DCs) are used as natural adjuvants for vaccination, but the factors that influence the efficacy of this treatment are poorly understood. We investigated the parameters that affect the migration of subcutaneously injected mouse-mature DCs to the draining lymph node. We found that the efficiency of DC migration varied with the number of injected DCs and that CCR7+/+ DCs migrating to the draining lymph node, but not CCR7−/− DCs that failed to do so, efficiently induced a rapid increase in lymph node cellularity, which was observed before the onset of T cell proliferation. We also report that DC migration could be increased up to 10-fold by preinjection of inflammatory cytokines that increased the expression of the CCR7 ligand CCL21 in lymphatic endothelial cells. The magnitude and quality of CD4+ T cell response was proportional to the number of antigen-carrying DCs that reached the lymph node and could be boosted up to 40-fold by preinjection of tumor necrosis factor that conditioned the tissue for increased DC migration. These results indicate that DC number and tissue inflammation are critical parameters for DC-based vaccination.
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                Author and article information

                Journal
                Theranostics
                Theranostics
                thno
                Theranostics
                Ivyspring International Publisher (Sydney )
                1838-7640
                2016
                2 September 2016
                : 6
                : 11
                : 2000-2014
                Affiliations
                [1 ]Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan 430074, China;
                [2 ]MoE Key Laboratory for Biomedical Photonics, Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan 430074, China;
                [3 ]Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan 430022, China.
                Author notes
                ✉ Corresponding author: Zhihong Zhang ( czyzzh@ 123456mail.hust.edu.cn ).

                *These authors are co-corresponding authors.

                Conflict of Interest: The authors declare no competing financial interests.

                Article
                thnov06p2000
                10.7150/thno.15102
                5039339
                27698936
                896c115f-d128-4176-b822-7917c7de0052
                © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
                History
                : 26 January 2016
                : 13 July 2016
                Categories
                Research Paper

                Molecular medicine
                dc vaccine,immunotherapy,antigen delivery,dc migration tracking,magnetic targeting.

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