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

676810

Sigma-Aldrich

Ethyl acetate, ACS reagent, ≥99.5%

199443

Sigma-Aldrich

Aluminum oxide, activated, basic, Brockmann I

199966

Sigma-Aldrich

Aluminum oxide, activated, acidic, Brockmann I

199974

Sigma-Aldrich

Aluminum oxide, activated, neutral, Brockmann I

T6508

Sigma-Aldrich

Trifluoroacetic acid, ReagentPlus^®, 99%

494453

Sigma-Aldrich

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

494518

Sigma-Aldrich

Ethyl acetate, biotech. grade, ≥99.8%

472301

Sigma-Aldrich

Dimethyl sulfoxide, ACS reagent, ≥99.9%

267740

Sigma-Aldrich

Aluminum oxide, pore size 58 Å, ~150 mesh

L092004

Sigma-Aldrich

Ethyl acetate

L092003

Sigma-Aldrich

Ethyl acetate

A1522

Sigma-Aldrich

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

91707

Sigma-Aldrich

Trifluoroacetic acid, puriss. p.a., suitable for HPLC, ≥99.0% (GC)

D5879

Sigma-Aldrich

Dimethyl sulfoxide, ReagentPlus^®, ≥99.5%

D65100

Sigma-Aldrich

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

319902

Sigma-Aldrich

Ethyl acetate, ACS reagent, ≥99.5%

320269

Sigma-Aldrich

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

299537

Sigma-Aldrich

Trifluoroacetic acid, ≥99%, for protein sequencing

650188

Sigma-Aldrich

Methanol solution, (Methanol:Dimethyl sulfoxide 1:1 (v/v))

642991

Sigma-Aldrich

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

718475

Sigma-Aldrich

Aluminum oxide, nanopowder, 13 nm primary particle size (TEM), 99.8% trace metals basis

721956

Sigma-Aldrich

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

702129

Sigma-Aldrich

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

634875

Sigma-Aldrich

Aluminum oxide, single crystal substrate, <0001>

342653

Sigma-Aldrich

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

234745

Sigma-Aldrich

Aluminum oxide, Corundum, α-phase, -100 mesh

342688

Sigma-Aldrich

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

229423

Sigma-Aldrich

Aluminum oxide, powder, 99.99% trace metals basis

233714

Sigma-Aldrich

Sodium bisulfate monohydrate, ReagentPlus^®, 99%

676853

Sigma-Aldrich

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