Reduction and Anticancer Activity of Platinum(IV) Complexes

Choi, Sunhee; Filotto, Catherine; Bisanzo, Mark; Delaney, Sarah; Lagasee, Daniel; Whitworth, Jennifer L.; Jusko, Andrew; Li, Chengruo; Wood, Nicole A.; Willingham, Jennifer; Schwenker, and Amy; Spaulding, Kathleen

doi:10.1021/ic971047x

Cited by 253 publications

(249 citation statements)

References 19 publications

(27 reference statements)

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“…These values indicate that the presence of the polymeric backbone does not significantly influence the electronic or steric environment of the tethered platinum center and that this construct will effectively release active cisplatin required for anticancer activity. The low values of the cathodic peak for PLA-Pt(IV) also augurs well for the clinical requirement that this construct not be prematurely released in blood (42,43).…”

Section: Resultsmentioning

confidence: 56%

Engineering of self-assembled nanoparticle platform for precisely controlled combination drug therapy

Kolishetti

Dhar

Valencia

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

537

429

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The genomic revolution has identified therapeutic targets for a plethora of diseases, creating a need to develop robust technologies for combination drug therapy. In the present work, we describe a self-assembled polymeric nanoparticle (NP) platform to target and control precisely the codelivery of drugs with varying physicochemical properties to cancer cells. As proof of concept, we codelivered cisplatin and docetaxel (Dtxl) to prostate cancer cells with synergistic cytotoxicity. A polylactide (PLA) derivative with pendant hydroxyl groups was prepared and conjugated to a platinum(IV) [Pt(IV)] prodrug, c,t,c-½PtðNH 3 Þ 2 ðO 2 CCH 2 CH 2 COOHÞðOHÞCl 2 [PLAPt(IV)]. A blend of PLA-Pt(IV) functionalized polymer and carboxylterminated poly(D,L-lactic-co-glycolic acid)-block-poly(ethylene glycol) copolymer in the presence or absence of Dtxl, was converted, in microfluidic channels, to NPs with a diameter of ∼100 nm. This process resulted in excellent encapsulation efficiency (EE) and high loading of both hydrophilic platinum prodrug and hydrophobic Dtxl with reproducible EEs and loadings. The surface of the NPs was derivatized with the A10 aptamer, which binds to the prostatespecific membrane antigen (PSMA) on prostate cancer cells. These NPs undergo controlled release of both drugs over a period of 48-72 h. Targeted NPs were internalized by the PSMA-expressing LNCaP cells via endocytosis, and formation of cisplatin 1,2-d(GpG) intrastrand cross-links on nuclear DNA was verified. In vitro toxicities demonstrated superiority of the targeted dual-drug combination NPs over NPs with single drug or nontargeted NPs. This work reveals the potential of a single, programmable nanoparticle to blend and deliver a combination of drugs for cancer treatment.chemotherapy | drug delivery | polymer-drug conjugate | targeting | temporal release

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Section: Resultsmentioning

confidence: 56%

Engineering of self-assembled nanoparticle platform for precisely controlled combination drug therapy

Kolishetti

Dhar

Valencia

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

537

429

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“…The knowledge of the reactivity of Pt(IV) compounds towards the reduction by potential bioreductant like ascorbic acid may be important for understanding the mechanism of where antitumor activity as well as for designing new compounds with the least side effect. Chois et al [17] reported that there is a correlation between the rate of the reduction and anticancer activity in a series of homologous Pt(IV) complex without going into the details of reaction mechanism. The present study was undertaken with the aim of extending the knowledge of the kinetics and thermodynamic parameters that characterized the reduction of Pt(IV) complex by ascorbic acid and clarifying the mechanism details using the model complex PtCl 6 2− .…”

Section: Introductionmentioning

confidence: 99%

Kinetics and Mechanism of Oxidation of L-Ascorbic Acid by Pt(IV)(aq) in Aqueous Hydrochloric Acid Medium

Senapati

Das

Patnaik

2012

Advances in Physical Chemistry

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Reduction of [PtCl 6 ] 2− by L-ascorbic acid (H 2 ASc) in 0.1 M aqueous acid medium has been investigated spectrophotometrically under pseudo-first order condition at [PtCl 6 The redox reaction follows the rate law:, where k is the second-order rate constant and [H 2 ASc] is the total concentration of ascorbic acid. Electron transfer from [H 2 ASc] to Pt(IV) center leading to the release of two halide ions and formation of the reaction products, square planner Pt(II) halide complex, and dehydrated ascorbic acid is suggested. This redox reaction follows an outersphere mechanism as Pt(IV) complex is substituted inert. Activation parameters were calculated corresponding to rate of electron transfer reaction k. Activation parameters favor the electron transfer reaction.

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“…The cathodic reduction potential depends on the electronwithdrawing power and the bulkiness of the axial and auxiliary ligands. The low reduction potential of mitaplatin is influenced by the presence of chlorine atoms from the DCA molecules near the platinum center (29).…”

mentioning

confidence: 99%