Abstract
Multidrug resistance (MDR) remains a major problem in cancer therapy and is characterized by the overexpression of p-glycoprotein (P-gp) efflux pump, upregulation of anti-apoptotic proteins or downregulation of pro-apoptotic proteins. In this study, an Apolipoprotein A1 (ApoA1)-modified cationic liposome containing a synthetic cationic lipid and cholesterol was developed for the delivery of a small-molecule chemotherapeutic drug, doxorubicin (Dox) to treat MDR tumor. The liposome-modified by ApoA1 was found to promote drug uptake and elicit better therapeutic effects than free Dox and liposome in MCF-7/ADR cells. Further, loading Dox into the present ApoA1-liposome systems enabled a burst release at the tumor location, resulting in enhanced anti-tumor effects and reduced off-target effects. More importantly, ApoA1-lip/Dox caused fewer adverse effects on cardiac function and other organs in 4T1 subcutaneous xenograft models. These features indicate that the designed liposomes represent a promising strategy for the reversal of MDR in cancer treatment.
Highlights
IntroductionPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
Apolipoprotein A1 (ApoA1)-lip/Dox and Lip/Dox liposomes were prepared with some modifications by incorporating the cationic phospholipid, (2,3-Dioleoyloxy-propyl)trimethylammonium-chloride (DOTAP), into the liposomal formulation
The results suggested that another main endocytosis pathways of ApoA1-lip/Dox was clathrin-mediated endocytosis
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Chemotherapy is one of the main therapeutic approaches for cancer treatment and includes the application of small-molecule drugs, such as anthracyclines, topoisomerase inhibitors and antimetabolites. The occurrence of multidrug resistance (MDR) is a major reason for the failure of chemotherapy [1]. The main cause of MDR is the increased efflux of anti-cancer drugs by membrane-embedded drug transporters [2]. The most common drug transporters including P-glycoprotein (P-gp), multidrug resistance protein 1 (MPR1), and breast cancer resistance protein (BCRP) belong to the ATP-Binding Cassette (ABC)
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