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

D2650

Sigma-Aldrich

Dimethyl sulfoxide, Hybri-Max^™, sterile-filtered, BioReagent, suitable for hybridoma, ≥99.7%

721956

Sigma-Aldrich

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

634875

Sigma-Aldrich

Aluminum oxide, single crystal substrate, <0001>

379115

Sigma-Aldrich

DCC, 1.0 M in methylene chloride

74875

Sigma-Aldrich

8-Octanoyloxypyrene-1,3,6-trisulfonic acid trisodium salt, suitable for fluorescence, ≥90% (HPCE)

436178

Sigma-Aldrich

1-Ethylpiperidine hypophosphite, 95%

448273

Sigma-Aldrich

4-Acryloylmorpholine, 97%, contains 1,000 ppm monomethyl ether hydroquinone as inhibitor

551643

Sigma-Aldrich

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

558257

Sigma-Aldrich

Calcium hydride, 99.9% trace metals basis

606723

Sigma-Aldrich

Methanol-¹²C, 99.95 atom % ¹²C

202606

Sigma-Aldrich

Aluminum oxide, 99.997% trace metals basis

702129

Sigma-Aldrich

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

494518

Sigma-Aldrich

Ethyl acetate, biotech. grade, ≥99.8%

A1522

Sigma-Aldrich

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

320269

Sigma-Aldrich

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

229423

Sigma-Aldrich

Aluminum oxide, powder, 99.99% trace metals basis

342688

Sigma-Aldrich

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

342653

Sigma-Aldrich

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

L092003

Sigma-Aldrich

Ethyl acetate

L092004

Sigma-Aldrich

Ethyl acetate

676853

Sigma-Aldrich

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

D65100

Sigma-Aldrich

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

676810

Sigma-Aldrich

Ethyl acetate, ACS reagent, ≥99.5%

319902

Sigma-Aldrich

Ethyl acetate, ACS reagent, ≥99.5%

D1435

Sigma-Aldrich

Dimethyl sulfoxide, meets EP testing specifications, meets USP testing specifications

D2438

Sigma-Aldrich

Dimethyl sulfoxide, sterile-filtered, BioPerformance Certified, meets EP, USP testing specifications, suitable for hybridoma

D4540

Sigma-Aldrich

Dimethyl sulfoxide, ≥99.5% (GC), suitable for plant cell culture

199966

Sigma-Aldrich

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

199443

Sigma-Aldrich

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

199974

Sigma-Aldrich

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