Nanostructured lipid carriers co-delivering lapachone and doxorubicin for overcoming multidrug resistance in breast cancer therapy

Abstract

Xin Li,1 Xiaoqian Jia,2 Hu Niu2 1Department of Breast and Thyroid Surgery, Heze Municipal Hospital, Heze, Shandong, China; 2Department of General Surgery 2, The Fourth People’s Hospital of Jinan, Jinan, Shandong, China Background: Multidrug resistance is responsible for the poor outcome in breast cancer therapy. Lapa is a novel therapeutic agent that generates ROS through the catalysis of the NAD(P)H:quinone oxidoreductase-1 (NQO1) enzyme which significantly facilitate the intracellular accumulation of the co-delivered DOX to overcome MDR in cancer cells. Purpose: Herein, in our study, nanostructured lipid carrier (NLC) co-delivering β-lapachone (Lapa) and doxorubicin (DOX) was developed (LDNLC) with the aim to overcome the multidrug resistance (MDR) in breast cancer therapy. Patients and methods: Lapa and DOX were loaded into NLC to prepare LDNLC using melted ultrasonic dispersion method. Results: The well designed LDNLC was nanoscaled particles that exhibited preferable stability in physiological environment. In vitro cell experiments on MCF-7 ADR cells showed increased DOX retention as compared to DOX mono-delivery NLC (DNLC). In vivo anti-cancer assays on MCF-7 ADR tumor bearing mice model also revealed significantly enhanced efficacy of LDNLC than mono-delivery NLCs (DNLC and LNLC). Conclusion: LDNLC might be a promising platform for effective breast cancer therapy. Keywords: β-lapachone, doxorubicin, nanostructured lipid carriers, multidrug resistance, breast cancer

Keywords

• β-lapachone
• doxorubicin
• nanostructured lipid carriers
• multidrug resistance
• breast cancer