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Design of a novel theranostic nanomedicine: Synthesis and physicochemical properties of a biocompatible Polyphosphazene–platinum(II) conjugate

Title
Design of a novel theranostic nanomedicine: Synthesis and physicochemical properties of a biocompatible Polyphosphazene–platinum(II) conjugate
Authors
Avaji P.G.Park J.H.Lee H.J.Jun Y.J.Park K.S.Lee K.E.Choi S.-J.Sohn Y.S.
Ewha Authors
손연수이화정
SCOPUS Author ID
손연수scopus; 이화정scopus
Issue Date
2016
Journal Title
International Journal of Nanomedicine
ISSN
1176-9114JCR Link
Citation
vol. 11, pp. 837 - 851
Keywords
Anticancer agentNanomedicineOxaliplatinPolyphosphazeneTheranostics
Publisher
Dove Medical Press Ltd.
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
To develop a theranostic nanomedicine involving the antitumor-active moiety (dach)Pt(II) (dach: trans-(±)-1,2-diaminocyclohexane) of oxaliplatin (OX), a new biocompat­ible polyphosphazene carrier polymer was designed by grafting with a methoxy poly(ethylene glycol) (MPEG) to increase duration of circulation in the blood and with aminoethanol (AE) as a spacer group. The antitumor (dach)Pt moiety was conjugated to the carrier polymer using cis-aconitic acid (AA) as a linker, resulting in a polymer conjugate formulated as [NP(MPEG550)(AE-AA)Pt(dach)]n, named “Polyplatin” (PP). PP was found to self-assemble into very stable polymeric nanoparticles with a mean diameter of 55.1 nm and a critical aggre­gation concentration of 18.5 mg/L in saline. PP could easily be labeled with a fluorescence dye such as Cy5.5 for imaging studies. The time-dependent ex vivo image studies on organ distributions and clearance of Cy-labeled PP have shown that PP accumulated in the tumor with high selectivity by the enhanced permeability and retention effect but was cleared out from all the major organs including the liver in about 4 weeks postinjection. Another time-dependent bioimaging study on distribution and clearance of PP in mouse kidney using laser ablation inductively coupled plasma mass spectroscopy has shown that PP accumulates much less in kidney and is more rapidly excreted than monomeric OX, which is in accord with the very low acute toxicity of PP as shown by its high LD50 value of more than 2000 mg/kg. The pharmacokinetic study of PP has shown that it has a much longer half-life (t1/2β) of 13.3 hours compared with the 5.21 hours of OX and about a 20 times higher area under the curve value of 42,850.8 ng h/mL compared with the 2,320.4 ng h/mL of OX. The nude mouse xenograft trials of PP against the gastric MKN-28 tumor cell line exhibited remarkably better tumor efficacy compared with OX at the higher tolerated dose, with lower systemic toxicity. © 2016 Avaji et al.
DOI
10.2147/IJN.S99917
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자연과학대학 > 화학·나노과학전공 > Journal papers
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