β-Lapachone Micellar Nanotherapeutics for Non–Small Cell Lung Cancer Therapy
Open Access
- 12 May 2010
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 70 (10), 3896-3904
- https://doi.org/10.1158/0008-5472.can-09-3995
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 nanocarrier, 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 (t1/2, ∼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 β-lap nanomedicine platform with enhanced safety, pharmacokinetics, and antitumor efficacy for the specific treatment of NSCLC tumors. Cancer Res; 70(10); 3896–904. ©2010 AACR.Keywords
Other Versions
This publication has 42 references indexed in Scilit:
- In vivo Off-Resonance Saturation Magnetic Resonance Imaging of αvβ3-Targeted Superparamagnetic NanoparticlesCancer Research, 2009
- Multifunctional Micellar Nanomedicine for Cancer TherapyExperimental Biology and Medicine, 2009
- Intratumoral Delivery of β-Lapachone via Polymer Implants for Prostate Cancer TherapyClinical Cancer Research, 2008
- β-Lapachone-containing PEG–PLA polymer micelles as novel nanotherapeutics against NQO1-overexpressing tumor cellsJournal of Controlled Release, 2007
- Nonhomologous End Joining Is Essential for Cellular Resistance to the Novel Antitumor Agent, β-LapachoneCancer Research, 2007
- An NQO1- and PARP-1-mediated cell death pathway induced in non-small-cell lung cancer cells by β-lapachoneProceedings of the National Academy of Sciences of the United States of America, 2007
- In vivo fate of unimers and micelles of a poly(ethylene glycol)-block-poly(caprolactone) copolymer in mice following intravenous administrationEuropean Journal of Pharmaceutics and Biopharmaceutics, 2007
- In Situ Observation of Reduction Behavior of Hemoglobin Molecules Adsorbed on Glass SurfaceIEICE Transactions on Electronics, 2006
- Hemolytic and Hemoxidative Activities inMycoplasma penetransInfection and Immunity, 2000