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      Enhanced In Vitro Magnetic Cell Targeting of Doxorubicin-Loaded Magnetic Liposomes for Localized Cancer Therapy

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          Abstract

          The lack of efficient targeting strategies poses significant limitations on the effectiveness of chemotherapeutic treatments. This issue also affects drug-loaded nanocarriers, reducing nanoparticles cancer cell uptake. We report on the fabrication and in vitro characterization of doxorubicin-loaded magnetic liposomes for localized treatment of liver malignancies. Colloidal stability, superparamagnetic behavior and efficient drug loading of our formulation were demonstrated. The application of an external magnetic field guaranteed enhanced nanocarriers cell uptake under cell medium flow in correspondence of a specific area, as we reported through in vitro investigation. A numerical model was used to validate experimental data of magnetic targeting, proving the possibility of accurately describing the targeting strategy and predict liposomes accumulation under different environmental conditions. Finally, in vitro studies on HepG2 cancer cells confirmed the cytotoxicity of drug-loaded magnetic liposomes, with cell viability reduction of about 50% and 80% after 24 h and 72 h of incubation, respectively. Conversely, plain nanocarriers showed no anti-proliferative effects, confirming the formulation safety. Overall, these results demonstrated significant targeting efficiency and anticancer activity of our nanocarriers and superparamagnetic nanoparticles entrapment could envision the theranostic potential of the formulation. The proposed magnetic targeting study could represent a valid tool for pre-clinical investigation regarding the effectiveness of magnetic drug targeting.

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          Most cited references63

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          Analysis of nanoparticle delivery to tumours

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            Cancer nanomedicine: progress, challenges and opportunities

            The intrinsic limits of conventional cancer therapies prompted the development and application of various nanotechnologies for more effective and safer cancer treatment, herein referred to as cancer nanomedicine. Considerable technological success has been achieved in this field, but the main obstacles to nanomedicine becoming a
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              Cisplatin in cancer therapy: molecular mechanisms of action.

              Cisplatin, cisplatinum, or cis-diamminedichloroplatinum (II), is a well-known chemotherapeutic drug. It has been used for treatment of numerous human cancers including bladder, head and neck, lung, ovarian, and testicular cancers. It is effective against various types of cancers, including carcinomas, germ cell tumors, lymphomas, and sarcomas. Its mode of action has been linked to its ability to crosslink with the purine bases on the DNA; interfering with DNA repair mechanisms, causing DNA damage, and subsequently inducing apoptosis in cancer cells. However, because of drug resistance and numerous undesirable side effects such as severe kidney problems, allergic reactions, decrease immunity to infections, gastrointestinal disorders, hemorrhage, and hearing loss especially in younger patients, other platinum-containing anti-cancer drugs such as carboplatin, oxaliplatin and others, have also been used. Furthermore, combination therapies of cisplatin with other drugs have been highly considered to overcome drug-resistance and reduce toxicity. This comprehensive review highlights the physicochemical properties of cisplatin and related platinum-based drugs, and discusses its uses (either alone or in combination with other drugs) for the treatment of various human cancers. A special attention is paid to its molecular mechanisms of action, and its undesirable side effects. Copyright © 2014 Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                Nanomaterials (Basel)
                Nanomaterials (Basel)
                nanomaterials
                Nanomaterials
                MDPI
                2079-4991
                23 October 2020
                November 2020
                : 10
                : 11
                : 2104
                Affiliations
                [1 ]The BioRobotics Institute and Department of Excellence in Robotics and AI, Scuola Superiore Sant’Anna, 56124 Pisa, Italy
                [2 ]Center for Micro-BioRobotics, Istituto Italiano di Tecnologia, Viale Rinaldo Piaggio 34 Pontedera, 56025 Pisa, Italy; agostina.grillone@ 123456iit.it (A.F.G.); alessio.mondini@ 123456iit.it (A.M.)
                [3 ]Institute of Clinical Physiology, CNR San Cataldo Research Area, Via Giuseppe Moruzzi 1, 56124 Pisa, Italy; serena@ 123456ifc.cnr.it
                [4 ]Institute for Advanced Research of Biosystem Dynamics, Research Institute for Science and Engineering, Waseda University, Tokyo 169-8050, Japan; tianshuli@ 123456aoni.waseda.jp (T.L.); takeoka@ 123456waseda.jp (S.T.)
                [5 ]School of Advanced Science and Engineering, Waseda University, Tokyo 169-8050, Japan
                Author notes
                Author information
                https://orcid.org/0000-0002-9755-3431
                https://orcid.org/0000-0003-3722-8861
                https://orcid.org/0000-0003-0001-8561
                https://orcid.org/0000-0002-4715-8353
                Article
                nanomaterials-10-02104
                10.3390/nano10112104
                7690690
                33114052
                0f1db42f-be17-4ac2-807e-241ca7598692
                © 2020 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
                : 25 September 2020
                : 20 October 2020
                Categories
                Article

                magnetic drug targeting,magnetic liposomes,nanomedicine

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