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已发表论文
基于表面活性剂的纳米粒子加载阿霉素以克服癌症中的多药抗药性
Authors Huang W, Lang Y, Hakeem Abdul, Lei Y, Gan L, Yang X
Received 17 November 2017
Accepted for publication 24 January 2018
Published 21 March 2018 Volume 2018:13 Pages 1723—1736
DOI https://doi.org/10.2147/IJN.S157368
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Govarthanan Muthusamy
Peer reviewer comments 2
Editor who approved publication: Dr Linlin Sun
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.
Keywords: multidrug resistance, cellular uptake, cellular efflux, biodistribution
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.
Keywords: multidrug resistance, cellular uptake, cellular efflux, biodistribution
