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

• Published in: International journal of nanomedicine Vol. 13; pp. 4107 - 4119
• Main Authors: Li, Xin, Jia, Xiaoqian, Niu, Hu
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01-01-2018; Taylor & Francis Ltd; Dove Medical Press
• Subjects: Acids; Adenosine Triphosphate - metabolism; Analysis; Animals; Anthracyclines; Antineoplastic agents; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cancer cells; Cancer therapies; Cancer treatment; Catalysis; Cell Death - drug effects; Cell Survival - drug effects; Chemotherapy; Colloids; Colorectal cancer; doxorubicin; Doxorubicin - pharmacology; Doxorubicin - therapeutic use; Drug Carriers - chemistry; Drug delivery systems; Drug Liberation; Drug resistance; Drug Resistance, Multiple - drug effects; Drug Resistance, Neoplasm - drug effects; Enzymes; Female; Health aspects; Hemolysis - drug effects; Humans; Kinases; Lipids; Lipids - chemistry; MCF-7 Cells; Mice, Inbred BALB C; Mice, Nude; Microbial drug resistance; multidrug resistance; Multidrug resistant organisms; Nanoparticles; nanostructured lipid carriers; Nanostructures - chemistry; Naphthoquinones - therapeutic use; Novels; Original Research; Particle Size; Physiological aspects; Polyethylene glycol; Quinones; Rabbits; Static Electricity; Tissue Distribution - drug effects; Tumor Burden - drug effects; Tumors; β-lapachone; United States > US; China; multidrug resistance; breast cancer; β-lapachone; doxorubicin; nanostructured lipid carriers
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S163929

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.
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.
Lapa and DOX were loaded into NLC to prepare LDNLC using melted ultrasonic dispersion method.
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).
LDNLC might be a promising platform for effective breast cancer therapy.