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

N4876

Sigma-Aldrich

Ninhydrin, suitable for amino acid detection

M2128

Sigma-Aldrich

Thiazolyl Blue Tetrazolium Bromide, 98%

M5655

Sigma-Aldrich

Thiazolyl Blue Tetrazolium Bromide, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥97.5% (HPLC)

D4551

Sigma-Aldrich

N,N-Dimethylformamide, ≥99%

T0886

Sigma-Aldrich

Triethylamine, ≥99%

C7559

Sigma-Aldrich

Chloroform, ≥99%, PCR Reagent, contains amylenes as stabilizer

W424601

Sigma-Aldrich

Triethylamine, ≥99.5%

90340

Sigma-Aldrich

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

90335

Sigma-Aldrich

Triethylamine, BioUltra, ≥99.5% (GC)

60339

Sigma-Aldrich

Potassium bicarbonate, BioUltra, ≥99.5% (T)

90337

Sigma-Aldrich

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

517747

Sigma-Aldrich

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

179272

Sigma-Aldrich

Diethyl ether

288306

Sigma-Aldrich

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

471283

Sigma-Aldrich

Triethylamine, ≥99.5%

372978

Sigma-Aldrich

Chloroform, anhydrous, contains amylenes as stabilizer, ≥99%

227056

Sigma-Aldrich

N,N-Dimethylformamide, anhydrous, 99.8%

296082

Sigma-Aldrich

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

151173

Sigma-Aldrich

Ninhydrin, ACS reagent

322415

Sigma-Aldrich

Methanol, anhydrous, 99.8%

296309

Sigma-Aldrich

1,4-Dioxane, anhydrous, 99.8%, contains <=25 ppm BHT as stabilizer

323381

Sigma-Aldrich

Hydrogen peroxide solution, contains ~200 ppm acetanilide as stabilizer, 3 wt. % in H₂O

24216

Sigma-Aldrich

Chloroform, contains ethanol as stabilizer, meets analytical specification of BP, 99-99.4% (GC)

717975

Sigma-Aldrich

Methanol

32203

Sigma-Aldrich

Diethyl ether, contains BHT as inhibitor, 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)

676934

Sigma-Aldrich

1,4-Dioxane, ACS reagent, ≥99.0%, contains <=25 ppm BHT as stabilizer

346144

Sigma-Aldrich

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

33147

Sigma-Aldrich

1,4-Dioxane, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99.5% (GC)

360481

Sigma-Aldrich

1,4-Dioxane, ACS reagent, ≥99.0%, contains ≤25 ppm BHT as stabilizer