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Synthesis of Aptamer-PEI-g-PEG Modified Gold Nanoparticles Loaded with Doxorubicin for Targeted Drug Delivery
Published on: June 23, 2020
Surfactin-based nanoparticles loaded with doxorubicin to overcome multidrug resistance in cancers
Wenjing Huang1, Yan Lang1, Abdul Hakeem1
1Department of Nanomedicine and Biopharmaceuticals, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
Background:
Multidrug resistance (MDR) is one of the major obstacles to successful cancer chemotherapy. Developing efficient strategies to reverse MDR remains a major challenge. Surfactin (SUR), a cyclic lipopeptide biosurfactant, has been found to display anticancer activity.
Methods:
In this paper, SUR was assembled by solvent-emulsion method to load the anticancer drug doxorubicin (DOX). The cytotoxicity of DOX-loaded SUR nanoparticles (DOX@SUR) against DOX-resistant human breast cancer MCF-7/ADR is measured by MTT assay. The cellular uptake and intracellular retention of DOX@SUR are determined by flow cytometry. The tumor accumulation and anticancer activity of DOX@SUR are evaluated in MCF-7/ADR-bearing nude mice.
Results:
DOX@SUR induce stronger cytotoxicity against DOX-resistant human breast cancer MCF-7/ADR cells compared to free DOX. DOX@SUR nanoparticles exhibit enhanced cellular uptake and decreased cellular efflux, which might be associated with reduced P-glycoprotein expression. After internalization into MCF-7/ADR cells by macropinocytosis- and caveolin-mediated endocytosis, DOX@SUR nanoparticles are colocalized with the lysosomes and translocated to the nucleus to exert cytotoxicity. Furthermore, in vivo animal experiment shows that the DOX@ SUR nanoparticles are accumulated more efficiently in tumors than free DOX. Meanwhile, DOX@SUR nanoparticles display stronger tumor inhibition activity and fewer side effects in MCF-7/ADR-bearing nude mice.
Conclusion:
This study indicates that SUR-based nanocarrier might present a promising platform to reverse MDR in cancer chemotherapy.
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