Targeted doxorubicin nanotherapy strongly suppressing growth of multidrug resistant tumor in mice.
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 subsequent DOX release triggered by dual stimuli (low pH and redox) inside the tumor. Given the promise of the multifunctional micelle mediated delivery on inhibition of MDR tumor growth, FA/DOX micelle platform is a much sought after goal for cancer chemotherapy, especially for cancers resistant to anticancer drugs.
['Nguyen|Dai Hai|DH|', 'Lee|Jung Seok|JS|', 'Bae|Jin Woo|JW|', 'Choi|Jong Hoon|JH|', 'Lee|Yunki|Y|', 'Son|Joo Young|JY|', 'Park|Ki Dong|KD|']
D000818:Animals D000970:Antineoplastic Agents D045744:Cell Line, Tumor D002470:Cell Survival D002626:Chemistry, Pharmaceutical D004317:Doxorubicin D004337:Drug Carriers D019008:Drug Resistance, Neoplasm D004705:Endocytosis D005260:Female D005434:Flow Cytometry D005492:Folic Acid D006801:Humans D006863:Hydrogen-Ion Concentration D061986:MCF-7 Cells D051379:Mice D008807:Mice, Inbred BALB C D008823:Micelles D008856:Microscopy, Fluorescence D053758:Nanoparticles D010084:Oxidation-Reduction D020442:Poloxamer D011092:Polyethylene Glycols
Doxorubicin Pluronic micelles Multidrug-resistant tumor Redox-sensitive pH-sensitive targeted chemotherapy