Reduction-sensitive tioguanine prodrug micelles

André J. Van Der Vlies, Urara Hasegawa, Jeffrey A. Hubbell

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Colloidal drug and prodrug conjugates have unique targeting characteristics for tumor vasculature from the blood and for the lymphatics draining a tissue injection site. Tioguanine and tioguanine-generating prodrugs have been investigated as anticancer and immunosuppressive agents, including use in cancer immunotherapy. Recently we developed block copolymers of poly(ethylene glycol)-bl-poly(propylene sulfide) that self-assemble in aqueous solutions to form micellar structures. Since the polymers carry a free terminal thiol group resulting from the ring-opening polymerization of the propylene sulfide monomer, we sought to prepare prodrug block copolymers with tioguanine linked by a reduction-sensitive disulfide bond. The synthesis involved a disulfide exchange between the oxidized form of tioguanine and the polymer. Spectroscopic data is presented to support the proposed reaction. The polymers self-assembled when dispersed in water to form tioguanine prodrug micelles with a size range between 18 and 40 nm that released tioguanine in response to cysteine and serum as shown spectroscopically. In comparison with a poly(ethylene glycol) prodrug polymer, we show that the rate of tioguanine release can be controlled by changing the poly(propylene sulfide) block length and that the tioguanine remains bioactive with cultured cells.

Original languageEnglish
Pages (from-to)2812-2818
Number of pages7
JournalMolecular Pharmaceutics
Volume9
Issue number10
DOIs
StatePublished - Dec 3 2012
Externally publishedYes

Fingerprint

Thioguanine
Prodrugs
Micelles
Polymers
Ethylene Glycol
Disulfides
Immunosuppressive Agents
Sulfhydryl Compounds
Polymerization
Antineoplastic Agents
Immunotherapy
Cysteine
Cultured Cells
Neoplasms
Injections
Water

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Molecular Medicine
  • Drug Discovery

Cite this

Van Der Vlies, A. J., Hasegawa, U., & Hubbell, J. A. (2012). Reduction-sensitive tioguanine prodrug micelles. Molecular Pharmaceutics, 9(10), 2812-2818. https://doi.org/10.1021/mp3001183

Reduction-sensitive tioguanine prodrug micelles. / Van Der Vlies, André J.; Hasegawa, Urara; Hubbell, Jeffrey A.

In: Molecular Pharmaceutics, Vol. 9, No. 10, 03.12.2012, p. 2812-2818.

Research output: Contribution to journalArticle

Van Der Vlies, AJ, Hasegawa, U & Hubbell, JA 2012, 'Reduction-sensitive tioguanine prodrug micelles', Molecular Pharmaceutics, vol. 9, no. 10, pp. 2812-2818. https://doi.org/10.1021/mp3001183
Van Der Vlies AJ, Hasegawa U, Hubbell JA. Reduction-sensitive tioguanine prodrug micelles. Molecular Pharmaceutics. 2012 Dec 3;9(10):2812-2818. https://doi.org/10.1021/mp3001183
Van Der Vlies, André J. ; Hasegawa, Urara ; Hubbell, Jeffrey A. / Reduction-sensitive tioguanine prodrug micelles. In: Molecular Pharmaceutics. 2012 ; Vol. 9, No. 10. pp. 2812-2818.
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