Beta-lapachone-containing PEG-PLA polymer micelles as novel nanotherapeutics against NQO1-overexpressing tumor cells
| Autor: | Elvin Blanco, Damon Sutton, Jinming Gao, Brent D. Weinberg, David A. Boothman, Ying Dong, Erik A. Bey |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Cell Survival Sonication Polyesters Pharmaceutical Science Antineoplastic Agents Micelle Article Polyethylene Glycols chemistry.chemical_compound Cell Line Tumor NAD(P)H Dehydrogenase (Quinone) Humans Particle Size Cytotoxicity Micelles Drug Carriers Chemistry Molecular biology Biochemistry Solubility Cell culture Drug delivery Nanoparticles Female Drug carrier Ethylene glycol DNA Damage Naphthoquinones |
| Zdroj: | Journal of controlled release : official journal of the Controlled Release Society. 122(3) |
| ISSN: | 1873-4995 |
| Popis: | Beta-lapachone (beta-lap) is a novel anticancer agent that is bioactivated by NADP(H): quinone oxidoreductase 1 (NQO1), an enzyme overexpressed in a variety of tumors. Despite its therapeutic promise, the poor aqueous solubility of beta-lap hinders its preclinical evaluation and clinical translation. Our objective was to develop beta-lap-containing poly(ethylene glycol)-block-poly(D,L-lactide) (PEG-PLA) polymer micelles for the treatment of NQO1-overexpressing tumors. Several micelle fabrication strategies were examined to maximize drug loading. A film sonication method yielded beta-lap micelles with relatively high loading density (4.7+/-1.0% to 6.5+/-1.0%) and optimal size (29.6+/-1.5 nm). Release studies in phosphate-buffered saline (pH 7.4) showed the time (t(1/2)) for 50% of drug release at 18 h. In vitro cytotoxicity assays were performed in NQO1-overexpressing (NQO1+) and NQO1-null (NQO1-) H596 lung, DU-145 prostate, and MDA-MB-231 breast cancer cells. Cytotoxicity data showed that after a 2 h incubation with beta-lap micelles, a marked increase in toxicity was shown in NQO1+ cells over NQO1- cells, resembling free drug both in efficacy and mechanism of cell death. In summary, these data demonstrate the potential of beta-lap micelles as an effective therapeutic strategy against NQO1-overexpressing tumor cells. |
| Databáze: | OpenAIRE |
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