β-lapachone micellar nanotherapeutics for non-small cell lung cancer therapy

Elvin Blanco, Erik A. Bey, Chalermchai Khemtong, Su Geun Yang, Jagadeesh Setti-Guthi, Huabing Chen, Chase W. Kessinger, Kevin A. Carnevale, William G. Bornmann, David A. Boothman, Jinming Gao

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

Lung cancer is the leading cause of cancer-related deaths with current chemotherapies lacking adequate specificity and efficacy. β-Lapachone (β-lap) is a novel anticancer drug that is bioactivated by NAD(P)H:quinone oxidoreductase 1, an enzyme found specifically overexpressed in non-small cell lung cancer (NSCLC). Herein, we report a nanotherapeutic strategy that targets NSCLC tumors in two ways: (a) pharmacodynamically through the use of a bioactivatable agent, β-lap, and (b) pharmacokinetically by using a biocompatible nano-carrier, polymeric micelles, to achieve drug stability, bioavailability, and targeted delivery. β-Lap micelles produced by a film sonication technique were small (∼30 nm), displayed core-shell architecture, and possessed favorable release kinetics. Pharmacokinetic analyses in mice bearing subcutaneous A549 lung tumors showed prolonged blood circulation (t 1/2, ∼28 h) and increased accumulation in tumors. Antitumor efficacy analyses in mice bearing subcutaneous A549 lung tumors and orthotopic Lewis lung carcinoma models showed significant tumor growth delay and increased survival. In summary, we have established a clinically viable â-lap nanomedicine platform with enhanced safety, pharmacokinetics, and antitumor efficacy for the specific treatment of NSCLC tumors.

Original languageEnglish (US)
Pages (from-to)3896-3904
Number of pages9
JournalCancer Research
Volume70
Issue number10
DOIs
StatePublished - May 15 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Blanco, E., Bey, E. A., Khemtong, C., Yang, S. G., Setti-Guthi, J., Chen, H., Kessinger, C. W., Carnevale, K. A., Bornmann, W. G., Boothman, D. A., & Gao, J. (2010). β-lapachone micellar nanotherapeutics for non-small cell lung cancer therapy. Cancer Research, 70(10), 3896-3904. https://doi.org/10.1158/0008-5472.CAN-09-3995