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      Drug Delivery Strategies for Platinum-Based Chemotherapy

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          Abstract

          Few chemotherapeutics have had such an impact on cancer management as cis-diamminedichloridoplatinum(II) (CDDP), also known as cisplatin. The first member of the platinum-based drug family, CDDP's potent toxicity in disrupting DNA replication has led to its widespread use in multidrug therapies, with particular benefit in patients with testicular cancers. However, CDDP also produces significant side effects that limit the maximum systemic dose. Various strategies have been developed to address this challenge including encapsulation within micro- or nanocarriers and the use of external stimuli such as ultrasound to promote uptake and release. The aim of this review is to look at these strategies and recent scientific and clinical developments.

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          Most cited references229

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          Principles of nanoparticle design for overcoming biological barriers to drug delivery.

          Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.
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            The resurgence of platinum-based cancer chemotherapy.

            The accidental discovery of the anticancer properties of cisplatin and its clinical introduction in the 1970s represent a major landmark in the history of successful anticancer drugs. Although carboplatin--a second-generation analogue that is safer but shows a similar spectrum of activity to cisplatin--was introduced in the 1980s, the pace of further improvements slowed for many years. However, in the past several years interest in platinum drugs has increased. Key developments include the elucidation of mechanisms of tumour resistance to these drugs, the introduction of new platinum-based agents (oxaliplatin, satraplatin and picoplatin), and clinical combination studies using platinum drugs with resistance modulators or new molecularly targeted drugs.
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              Platinum Compounds: a New Class of Potent Antitumour Agents

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                Author and article information

                Contributors
                (View ORCID Profile)
                (View ORCID Profile)
                Journal
                ACS Nano
                ACS Nano
                American Chemical Society (ACS)
                1936-0851
                1936-086X
                September 26 2017
                August 31 2017
                September 26 2017
                : 11
                : 9
                : 8560-8578
                Affiliations
                [1 ]Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford OX1 2JD, United Kingdom
                [2 ]Department of Nanobiomedical Science and BK21 Plus NBM, Global Research Center for Regenerative Medicine, Dankook University, 518-10 Anseo-dong, Dongnam-gu, Cheonan, Chungcheongnam-do, Republic of Korea
                [3 ]The Discoveries Centre for Regenerative and Precision Medicine, UCL Campus, Gower Street, London WC1E 6BT, United Kingdom
                Article
                10.1021/acsnano.7b04092
                28829568
                3e487b2b-d3ad-4340-88f6-151b55c18353
                © 2017
                History

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