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WIREs Nanomed Nanobiotechnol
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Multifunctional platinum‐based nanoparticles for biomedical applications

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Platinum‐based anticancer drugs play a central role in current cancer therapy. However, their applicability and efficacy are limited by drug resistance and adverse effects. Nanocarrier‐based platinum drug delivery systems are promising alternatives to circumvent the disadvantages of bare platinum drugs. The various properties of nanoparticle chemistry allow for the trend toward multiple functionality. Nanoparticles preferentially accumulate at the tumor site through passive targeting, and the attachment of tumor targeting moieties further enhances their tumor‐specific localization as well as tumor cell uptake. The introduction of stimuli‐responsive groups into drug delivery systems can further achieve spatially and temporally controlled drug release in response to specific stimuli. Combination therapy strategies have been used to promote synergetic efficacy and overcome the resistance of platinum drugs. The tumor‐localized drug delivery strategies exhibit benefits for preventing local tumor recurrence. In addition, the combination of platinum drugs and imaging agents in one unity allows the cancer diagnostics for real‐time monitoring the distribution of drug‐loaded nanoparticles inside the body and tumor. This review discusses recent scientific advances in multifunctional nanoparticle formulations of platinum drugs, and these designs exhibit new potential of multifunctional nanoparticles for delivering platinum‐based anticancer drugs. WIREs Nanomed Nanobiotechnol 2017, 9:e1410. doi: 10.1002/wnan.1410 This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Schematic illustration of the successive steps of multivalent binding and internalization of targeted protocells, followed by endosomal escape and nuclear localization of protocell‐encapsulated therapeutic (drugs, small interfering RNA, and toxins) and diagnostic (quantum dots) agents. (Reprinted with permission from Ref . Copyright 2011 Nature Publishing Group)
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Generalized scheme showing the work process of the oxaliplatin‐loaded AMPN mats in the human body to prevent tumor recurrence after hepatocellular carcinoma surgery. (Reprinted with permission from Ref . Copyright 2015 Elsevier Inc.)
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Schematic illustration showing the plausible combination therapeutic effect of cisplatin and poly(I:C) co‐loaded micelles. (Reprinted with permission from Ref . Copyright 2015 John Wiley & Sons, Inc.)
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(a) Schematic illustration showing the preparation of cRGD‐M(DTX/Pt) micelles. (b) cRGD‐M(DTX/Pt) micelles enter tumor cells through receptor‐mediated endocytosis, and the two drugs loaded act synergistically intracellularly. (Reprinted with permission from Ref . Copyright 2013 Elsevier Ltd.)
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(a) Generalized scheme showing the formation of PSQ particles from the Pt (IV) precursor and the release mechanism of active Pt(II) agent from PSQ particles. (b) Schematic illustration of the preparation of PEG‐P(LG‐DTDP‐Pt) micelles and the possible mechanism of their action. (Reprinted with permission from Refs . Copyright 2011 John Wiley & Sons, Inc. and Copyright 2015 Elsevier Ltd.)
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(a) Schematic illustration of the preparation of pH‐sensitiveNP/[email protected]‐DA nanoparticles with a core‐shell‐corona structure; (b) plasma concentration‐time profiles after intravenous injection of free cisplatin, NP/Pt orNP/[email protected]‐DA; (c) cellular uptake of FITC‐labeled NP/[email protected] PPC‐DA by A549R cells observed by confocal laser scanning microscopy; (d) platinum contamination in tumor tissue by quantitative analysis; (e) in vivo antitumor effect of NP/[email protected] PPC‐DA, compared with PBS control, free cisplatin and NP/Pt. (Reprinted with permission from Ref . Copyright 2014 John Wiley & Sons, Inc.)
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Several pH‐sensitive platinum drugs loaded nanoparticles for cancer therapy. (a and b) pH‐dependent release of cisplatin from Pt‐PHNPs and the cytotoxicity of cisplatin, Pt‐PHNPs, and Her‐Pt‐PHNPs against SK‐BR‐3 cells; (c and d) cisplatin release profile from PEG‐PLGA‐Pt(IV) nanoparticles at pH = 5.0, pH = 6.0, and pH = 7.4 PBS buffer at 37°C and cell viabilities determined by MTT assay of A2780 human ovarian carcinoma cell line treated with cell media, PEG‐PLA nanoparticles, free cisplatin and PEG‐PLGA‐Pt(IV) nanoparticles; (e and f) pH‐responsive drug release from Pt‐HSA/Ca P nanoparticles and redox‐ responsive release of Pt (II) drug from Pt‐HSA and DNA platination. (Reprinted with permission from Refs . Copyright 2009 American Chemical Society, Copyright 2009 American Chemical Society and Copyright 2015 John Wiley & Sons, Inc.)
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