Abstract
β-Lapachone (β-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 β-lap hinders its preclinical evaluation and clinical translation. Our objective was to develop β-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 β-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 (t1/2) 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 β-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 β-lap micelles as an effective therapeutic strategy against NQO1-overexpressing tumor cells.
Original language | English (US) |
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Pages (from-to) | 365-374 |
Number of pages | 10 |
Journal | Journal of Controlled Release |
Volume | 122 |
Issue number | 3 |
DOIs | |
State | Published - Oct 8 2007 |
Keywords
- Cancer nanomedicine
- Drug delivery
- Poly(ethylene glycol)-poly(d,l-lactide) (PEG-PLA)
- Polymer micelles
- β-Lapachone
ASJC Scopus subject areas
- Pharmaceutical Science