Targeted doxorubicin nanotherapy strongly suppressing growth of multidrug resistant tumor in mice

International Journal of Pharmaceutics
Dai Hai NguyenKi Dong Park

Abstract

The rational design of nanomedicine to treat multidrug resistant (MDR) tumors in vivo is described in the study. We prepared multifunctionalized Pluronic micelles that are already well-established to be responsive to low pH and redox in order to systemically deliver doxorubicin (DOX) to MDR tumors. Folic acids (FAs) were introduced on the micelle surface as tumor-targeting molecules. In vitro, the DOX-loaded micelles exerted high cytotoxicity in the DOX-resistant cells by bypassing MDR efflux. Cellular uptake studies clearly demonstrated that FA-conjugated DOX micelles (FA/DOX micelles) were efficiently internalized and accumulated in the MDR cells. In vivo studies indicated significant efficacy of FA/DOX micelles for MDR tumors in mice, and that the volume of tumors was 3 times smaller in this group than that of tumors in the free DOX group, and 8 times smaller than the tumors in the saline group. To the best of our knowledge, this methodology has been recognized to have significantly high efficacy, compared to previously reported DOX nanoparticle formulations. This superior anti-tumor efficacy of FA/DOX micelles in MDR tumor-bearing mice can be attributed to FA-targeted and -mediated endocytosis, inhibition of MDR effect, and...Continue Reading

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Citations

Oct 25, 2016·Materials Science & Engineering. C, Materials for Biological Applications·Thu Thao Nguyen ThiDai Hai Nguyen
May 12, 2017·Nano Convergence·Teruyuki Nagamune
Oct 21, 2016·Expert Opinion on Drug Delivery·Wing-Hin LeeRamin Rohanizadeh
Jul 28, 2016·International Journal of Molecular Sciences·Wei LiuWeisan Pan
Mar 24, 2017·International Journal of Biomaterials·Thi Lan NguyenDai Hai Nguyen
Mar 16, 2017·Artificial Cells, Nanomedicine, and Biotechnology·Saeideh AbdolahpourMaliheh Paknejad
May 1, 2021·International Journal of Molecular Sciences·Vrinda GoteDhananjay Pal

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