Hydrolysis-Sensitive Dithiolethione Prodrug Micelles.

Hydrolysis-Sensitive Dithiolethione Prodrug Micelles.

Macromolecular bioscience (2015-06-24)

Urara Hasegawa, Naoya Tateishi, Hiroshi Uyama, André J van der Vlies

ABSTRACT

Prodrug micelles carrying 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH), a compound possessing chemopreventive properties, are prepared from amphiphilic block copolymers linking ADT-OH via an ester bond using glycine (PAM-PGlyADT) and isoleucine linkers (PAM-PIleADT). The release of ADT-OH from the PAM-PIleADT micelles is much slower than the PAM-PGlyADT micelles. The PAM-PGlyADT micelles show comparable toxicity with ADT-OH in different cancer cell lines, whereas the PAM-PIleADT micelles are not toxic up to 400 µM. This ADT-ester prodrug micelle approach enables to modulate the release rate of ADT-OH and thus might find application in cancer therapy and prevention.

MATERIALS

Product Number

Brand

Product Description

717975

Sigma-Aldrich

Methanol, NMR reference standard

13464

Sigma-Aldrich

Sodium sulfate, puriss., meets analytical specification of Ph. Eur., BP, USP, anhydrous, 99.0-100.5% (calc. to the dried substance)

676780

Sigma-Aldrich

Methanol, ACS reagent, ≥99.8%

431583

Sigma-Aldrich

Potassium bicarbonate, ≥99.95% trace metals basis, 99.7-100.5% dry basis

24229

Sigma-Aldrich

Methanol, puriss., meets analytical specification of Ph Eur, ≥99.7% (GC)

346144

Sigma-Aldrich

Diethyl ether, reagent grade, ≥98%, contains ≤2% ethanol and ≤10ppm BHT as inhibitor

496189

Sigma-Aldrich

Chloroform, biotech. grade, ≥99.8%, contains 0.5-1.0% ethanol as stabilizer

494488

Sigma-Aldrich

N,N-Dimethylformamide, biotech. grade, ≥99.9%

32213

Sigma-Aldrich

Methanol, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99.8% (GC)

12602

Sigma-Aldrich

Potassium bicarbonate, puriss., meets analytical specification of Ph. Eur., BP, USP, E501, 99.5-101.0% (acidimetric)

793531

Sigma-Aldrich

Sodium sulfate, anhydrous, free-flowing, Redi-Dri^™, ReagentPlus^®, ≥99%

746363

Sigma-Aldrich

Sodium sulfate, anhydrous, free-flowing, Redi-Dri^™, ACS reagent, ≥99%

322415

Sigma-Aldrich

Methanol, anhydrous, 99.8%

517747

Sigma-Aldrich

Aluminum oxide, mesoporous, MSU-X (wormhole), average pore size 3.8 nm

179272

Sigma-Aldrich

Diethyl ether

90337

Sigma-Aldrich

Triethylamine, for amino acid analysis, ≥99.5% (GC)

90335

Sigma-Aldrich

Triethylamine, BioUltra, ≥99.5% (GC)

288306

Sigma-Aldrich

Chloroform, anhydrous, ≥99%, contains 0.5-1.0% ethanol as stabilizer

296082

Sigma-Aldrich

Diethyl ether, contains 1 ppm BHT as inhibitor, anhydrous, ≥99.7%

239313

Sigma-Aldrich

Sodium sulfate, ACS reagent, ≥99.0%, anhydrous, granular

71959

Sigma-Aldrich

Sodium sulfate, BioUltra, anhydrous, ≥99.0% (T)

T0886

Sigma-Aldrich

Triethylamine, ≥99%

W424601

Sigma-Aldrich

Triethylamine, ≥99.5%

90340

Sigma-Aldrich

Triethylamine, puriss. p.a., ≥99.5% (GC)

471283

Sigma-Aldrich

Triethylamine, ≥99.5%

90338

Sigma-Aldrich

Triethylamine, for protein sequence analysis, ampule, ≥99.5% (GC)

60339

Sigma-Aldrich

Potassium bicarbonate, BioUltra, ≥99.5% (T)

237205

Sigma-Aldrich

Potassium bicarbonate, ACS reagent, 99.7%, powder, crystals or granules

D4551

Sigma-Aldrich

N,N-Dimethylformamide, for molecular biology, ≥99%

151173

Sigma-Aldrich

Ninhydrin, ACS reagent