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

摘要

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.