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%

634875

Sigma-Aldrich

Aluminum oxide, single crystal substrate, <0001>

I15602

Sigma-Aldrich

Isobutyronitrile, 99%

276855

Sigma-Aldrich

Dimethyl sulfoxide, anhydrous, ≥99.9%

379115

Sigma-Aldrich

DCC, 1.0 M in methylene chloride

270989

Sigma-Aldrich

Ethyl acetate, anhydrous, 99.8%

538248

Sigma-Aldrich

Isobutyronitrile, 99.6%

436178

Sigma-Aldrich

1-Ethylpiperidine hypophosphite, 95%

448273

Sigma-Aldrich

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

439223

Sigma-Aldrich

Dichloromethane, suitable for HPLC, ≥99.9%, contains 40-150 ppm amylene as stabilizer

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

270997

Sigma-Aldrich

Dichloromethane, anhydrous, ≥99.8%, contains 40-150 ppm amylene as stabilizer

673439

Sigma-Aldrich

Dimethyl sulfoxide solution, 50 wt. % in H₂O

702129

Sigma-Aldrich

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

24233

Sigma-Aldrich

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

494518

Sigma-Aldrich

Ethyl acetate, biotech. grade, ≥99.8%

41640

Sigma-Aldrich

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

A6139

Sigma-Aldrich

Aluminum oxide, Type CG-20

A1522

Sigma-Aldrich

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

265497

Sigma-Aldrich

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

27227

Sigma-Aldrich

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

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

342718

Sigma-Aldrich

Aluminum oxide, calcined, powder, primarily α-phase, 100-325 mesh

45760

Sigma-Aldrich

Ethyl acetate, puriss. p.a., ACS reagent, ≥99.5% (GC)

34943

Sigma-Aldrich

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