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WIREs Nanomed Nanobiotechnol
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Nanoparticle formulations of cisplatin for cancer therapy

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The genotoxic agent cisplatin, used alone or in combination with radiation and/or other chemotherapeutic agents, is an important first‐line chemotherapy for a broad range of cancers. The clinical utility of cisplatin is limited both by intrinsic and acquired resistance and dose‐limiting normal tissue toxicity. That cisplatin shows little selectivity for tumor versus normal tissue may be a critical factor limiting its value. To overcome the low therapeutic ratio of the free drug, macromolecular, liposomal, and nanoparticle drug delivery systems have been explored toward leveraging the enhanced permeability and retention effect and promoting delivery of cisplatin to tumors. Here, we survey recent advances in nanoparticle formulations of cisplatin, focusing on agents that show promise in preclinical or clinical settings. WIREs Nanomed Nanobiotechnol 2016, 8:776–791. doi: 10.1002/wnan.1390 This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Schematic representation of the cisplatin‐loaded PLGA–PEG NPs, and intracellular reduction of Pt(IV) prodrug for the release of active cisplatin in PSMA expressing human prostate cancer LNCaP cells after receptor‐mediated endocytosis.
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Nanoparticle formulations used for cisplatin delivery.
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(a) Cisplatin prodrug was attached onto the framework after synthesis. (Reprinted with permission from Ref . Copyright 2014 American Chemical Society). (b) Cisplatin prodrug was incorporated within NCPs through use of the prodrug as the building block. (Reprinted with permission from Ref . Copyright 2014 Nature Publishing Group)
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Synthesis of lipid bilayer‐coated cisplatin NPs using a reverse microemulsion method. (Reprinted with permission from Ref . Copyright 2014 Elsevier)
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(a) Chemical structure of AP5280. (b) Schematic diagram of structural components showing the HPMA copolymer carrier, the tetrapeptide linker, and the N,O‐chelated platinum(II) diammine complex. Activity of AP5280 in the murine B16F10 tumor model: (c) Tumor volume and (d) animal weight as a function of time. (◆) Vehicle; (■) CBDCA 32 mg Pt/kg; (▲) AP5280 200 mg Pt/kg. (Reprinted with permission from Ref . Copyright 2004 Elsevier)
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Chemical structures of cisplatin and PEG–P(Glu) copolymer, and the formation and dissociation of cisplatin‐incorporating polymeric micelles (NC‐6004).
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Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

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