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      Doxorubicin loaded dual pH- and thermo-responsive magnetic nanocarrier for combined magnetic hyperthermia and targeted controlled drug delivery applications

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          Abstract

          Dual pH- and thermo-responsive magnetic nanocomposite as a platform for hyperthermia and controlled drug delivery in cancer treatment.

          Abstract

          Magnetic nanocarriers have attracted increasing attention for multimodal cancer therapy due to the possibility to deliver heat and drugs locally. The present study reports the development of magnetic nanocomposites (MNCs) made of an iron oxide core and a pH- and thermo-responsive polymer shell, that can be used as both hyperthermic agent and drug carrier. The conjugation of anticancer drug doxorubicin (DOX) to the pH- and thermo-responsive MNCs via acid-cleavable imine linker provides advanced features for the targeted delivery of DOX molecules via the combination of magnetic targeting, and dual pH- and thermo-responsive behaviour which offers spatial and temporal control over the release of DOX. The iron oxide cores exhibit a superparamagnetic behaviour with a saturation magnetization around 70 emu g −1. The MNCs contained 8.1 wt% of polymer and exhibit good heating properties in an alternating magnetic field. The drug release experiments confirmed that only a small amount of DOX was released at room temperature and physiological pH, while the highest drug release of 85.2% was obtained after 48 h at acidic tumour pH under hyperthermia conditions (50 °C). The drug release kinetic followed Korsmeyer–Peppas model and displayed Fickian diffusion mechanism. From the results obtained it can be concluded that this smart magnetic nanocarrier is promising for applications in multi-modal cancer therapy, to target and efficiently deliver heat and drug specifically to the tumour.

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          Most cited references51

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          Hyperthermia in combined treatment of cancer.

          Hyperthermia, the procedure of raising the temperature of tumour-loaded tissue to 40-43 degrees C, is applied as an adjunctive therapy with various established cancer treatments such as radiotherapy and chemotherapy. The potential to control power distributions in vivo has been significantly improved lately by the development of planning systems and other modelling tools. This increased understanding has led to the design of multiantenna applicators (including their transforming networks) and implementation of systems for monitoring of E-fields (eg, electro-optical sensors) and temperature (particularly, on-line magnetic resonance tomography). Several phase III trials comparing radiotherapy alone or with hyperthermia have shown a beneficial effect of hyperthermia (with existing standard equipment) in terms of local control (eg, recurrent breast cancer and malignant melanoma) and survival (eg, head and neck lymph-node metastases, glioblastoma, cervical carcinoma). Therefore, further development of existing technology and elucidation of molecular mechanisms are justified. In recent molecular and biological investigations there have been novel applications such as gene therapy or immunotherapy (vaccination) with temperature acting as an enhancer, to trigger or to switch mechanisms on and off. However, for every particular temperature-dependent interaction exploited for clinical purposes, sophisticated control of temperature, spatially as well as temporally, in deep body regions will further improve the potential.
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            Superparamagnetic iron oxide nanoparticles (SPIONs): development, surface modification and applications in chemotherapy.

            At present, nanoparticles are used for various biomedical applications where they facilitate laboratory diagnostics and therapeutics. More specifically for drug delivery purposes, the use of nanoparticles is attracting increasing attention due to their unique capabilities and their negligible side effects not only in cancer therapy but also in the treatment of other ailments. Among all types of nanoparticles, biocompatible superparamagnetic iron oxide nanoparticles (SPIONs) with proper surface architecture and conjugated targeting ligands/proteins have attracted a great deal of attention for drug delivery applications. This review covers recent advances in the development of SPIONs together with their possibilities and limitations from fabrication to application in drug delivery. In addition, the state-of-the-art synthetic routes and surface modification of desired SPIONs for drug delivery purposes are described. Copyright © 2010 Elsevier B.V. All rights reserved.
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              Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging.

              Magnetic nanoparticles (MNPs) represent a class of non-invasive imaging agents that have been developed for magnetic resonance (MR) imaging. These MNPs have traditionally been used for disease imaging via passive targeting, but recent advances have opened the door to cellular-specific targeting, drug delivery, and multi-modal imaging by these nanoparticles. As more elaborate MNPs are envisioned, adherence to proper design criteria (e.g. size, coating, molecular functionalization) becomes even more essential. This review summarizes the design parameters that affect MNP performance in vivo, including the physicochemical properties and nanoparticle surface modifications, such as MNP coating and targeting ligand functionalizations that can enhance MNP management of biological barriers. A careful review of the chemistries used to modify the surfaces of MNPs is also given, with attention paid to optimizing the activity of bound ligands while maintaining favorable physicochemical properties. Copyright 2009 Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                NANOHL
                Nanoscale
                Nanoscale
                Royal Society of Chemistry (RSC)
                2040-3364
                2040-3372
                2016
                2016
                : 8
                : 24
                : 12152-12161
                Affiliations
                [1 ]Biophysics Group
                [2 ]Department of Physics & Astronomy
                [3 ]University College London
                [4 ]London, UK
                [5 ]UCL Healthcare Biomagnetic and Nanomaterials Laboratories
                [6 ]School of Chemical Engineering
                [7 ]The University of New South Wales
                [8 ]Sydney, Australia
                [9 ]Australian Centre for Nanomedicine and Centre for Advanced Macromolecular Design
                [10 ]School of Materials Science
                [11 ]Japan Advanced Institute of Science and Technology
                [12 ]Nomi, Japan
                Article
                10.1039/C5NR07773G
                26892588
                95d0f372-3d5a-4f51-bbec-9728a464409e
                © 2016
                History

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