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

S5640

Sigma-Aldrich

Sodium sulfate, ≥99.0%, suitable for plant cell culture

S6547

Sigma-Aldrich

Sodium sulfate, BioXtra, ≥99.0%

C7559

Sigma-Aldrich

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

T0886

Sigma-Aldrich

Triethylamine, ≥99%

D4551

Sigma-Aldrich

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

M1775

Sigma-Aldrich

Methanol, Absolute - Acetone free

746363

Sigma-Aldrich

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

154903

Sigma-Aldrich

Methanol, ACS spectrophotometric grade, ≥99.9%

676845

Sigma-Aldrich

Diethyl ether, ACS reagent, ≥98.0%, contains ≤2% ethanol and ≤10ppm BHT as inhibitor

676780

Sigma-Aldrich

Methanol, ACS reagent, ≥99.8%

132950

Sigma-Aldrich

Chloroform, ReagentPlus^®, ≥99.8%, contains 0.5-1.0% ethanol as stabilizer

13464

Sigma-Aldrich

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

676934

Sigma-Aldrich

1,4-Dioxane, ACS reagent, ≥99.0%

D201863

Sigma-Aldrich

1,4-Dioxane, ReagentPlus^®, ≥99%, contains ≤25 ppm BHT as stabilizer

C2432

Sigma-Aldrich

Chloroform, contains 100-200 ppm amylenes as stabilizer, ≥99.5%

494437

Sigma-Aldrich

Methanol, BioReagent, ≥99.93%

431583

Sigma-Aldrich

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

24216

Sigma-Aldrich

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

24229

Sigma-Aldrich

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

239313

Sigma-Aldrich

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

494488

Sigma-Aldrich

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

366919

Sigma-Aldrich

Chloroform, ACS spectrophotometric grade, ≥99.8%, contains 0.5-1.0% ethanol as stabilizer

319988

Sigma-Aldrich

Chloroform, contains ethanol as stabilizer, ACS reagent, ≥99.8%

32203

Sigma-Aldrich

Diethyl ether, contains BHT as inhibitor, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99.8% (GC)

237205

Sigma-Aldrich

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

323381

Sigma-Aldrich

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

32211

Sigma-Aldrich

Chloroform, puriss. p.a., reag. ISO, reag. Ph. Eur., 99.0-99.4% (GC)

S9627

Sigma-Aldrich

Sodium sulfate, ReagentPlus^®, ≥99.0%

D158550

Sigma-Aldrich

N,N-Dimethylformamide, ReagentPlus^®, ≥99%

12602

Sigma-Aldrich

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