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

342653

Sigma-Aldrich

Aluminum oxide, fused, powder, primarily α-phase, 100-200 mesh

551643

Sigma-Aldrich

Aluminum oxide, nanowires, diam. × L 2-6 nm × 200-400 nm

721956

Sigma-Aldrich

Methanol solution, 4% in methanol-d₄ (99.8 atom % D), NMR tube size 3 mm × 8 in.

723851

Supelco

Dichloromethane solution, contains 10 % (v/v) methanol

702129

Sigma-Aldrich

Aluminum oxide, nanoparticles, <50 nm particle size (DLS), 20 wt. % in isopropanol

436178

Sigma-Aldrich

1-Ethylpiperidine hypophosphite, 95%

634875

Sigma-Aldrich

Aluminum oxide, single crystal substrate, <0001>

632546

Supelco

Methanol solution, contains 0.10 % (v/v) formic acid, UHPLC, suitable for mass spectrometry (MS), ≥99.5%

676810

Sigma-Aldrich

Ethyl acetate, ACS reagent, ≥99.5%

676853

Sigma-Aldrich

Dichloromethane, ACS reagent, ≥99.5%, contains 40-150 ppm amylene as stabilizer

642991

Sigma-Aldrich

Aluminum oxide, nanoparticles, 30-60 nm particle size (TEM), 20 wt. % in H₂O

265497

Sigma-Aldrich

Aluminum oxide, powder, primarily α phase, ≤10 μm avg. part. size, 99.5% trace metals basis

D65100

Sigma-Aldrich

Dichloromethane, contains 40-150 ppm amylene as stabilizer, ACS reagent, ≥99.5%

199966

Sigma-Aldrich

Aluminum oxide, Brockmann I, standard grade, activated, acidic

199974

Sigma-Aldrich

Aluminum oxide, activated, Brockmann I, standard grade, neutral

A1522

Sigma-Aldrich

Aluminum oxide, Type WN-6, Neutral, Activity Grade Super I

199443

Sigma-Aldrich

Aluminum oxide, standard grade, Brockmann I, activated, basic

267740

Sigma-Aldrich

Aluminum oxide, pore size 58 Å, ~150 mesh

27227

Sigma-Aldrich

Ethyl acetate, puriss., meets analytical specification of Ph. Eur., BP, NF, ≥99.5% (GC)

342688

Sigma-Aldrich

Aluminum oxide, fused, powder, primarily α-phase, -325 mesh

229423

Sigma-Aldrich

Aluminum oxide, powder, 99.99% trace metals basis

24233

Sigma-Aldrich

Dichloromethane, puriss., meets analytical specification of Ph. Eur., NF, ≥99% (GC)

494453

Sigma-Aldrich

Dichloromethane, biotech. grade, 99.9%, contains 40-150 ppm amylene as stabilizer

799300

Sigma-Aldrich

Aluminum oxide, Brockmann I, activated, standard grade, free-flowing, Redi-Dri^™

494518

Sigma-Aldrich

Ethyl acetate, biotech. grade, ≥99.8%

41640

Sigma-Aldrich

Dimethyl sulfoxide, puriss. p.a., ACS reagent, ≥99.9% (GC)

34943

Sigma-Aldrich

Dimethyl sulfoxide, puriss. p.a., dried, ≤0.02% water

799319

Sigma-Aldrich

Aluminum oxide, Brockmann I, standard grade, activated, neutral, free-flowing, Redi-Dri^™

320269

Sigma-Aldrich

Dichloromethane, ACS reagent, ≥99.5%, contains 40-150 ppm amylene as stabilizer

33211

Sigma-Aldrich

Ethyl acetate, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99.5% (GC)