title: Chemosensitization of doxorubicin in multidrug-resistant cells by unimolecular micelles via increased cellular accumulation and apoptosis.
abstract: OBJECTIVE
  Unimolecular micelles were prepared by modification of polyamidoamine (PAMAM) dendrimers using Pluronic F127 (PF127), which is expected to reverse multidrug resistance (MDR). And the reversal mechanisms have been studied.
  
  
  METHODS
  Characterization of the products was carried on. MTT assay was used to evaluate the cytotoxicity of the DOX-loaded conjugates. Cellular uptake study was measured by confocal laser scanning microscope and flow cytometry. Apoptosis assay was identified by Annexin V-FITC/PI apoptosis assay and Hoechst 33 342 staining.
  
  
  RESULTS
  Improved cytotoxicity of DOX-loaded conjugates in MCF-7/ADR cells (as much as 33-fold according to the IC50 values) was observed in contrast with that of free DOX. The DOX-loaded conjugates induced a much quicker and 100% uptake in MCF-7/ADR cells, and more than fivefold accumulation of DOX-loaded conjugates was observed compared with free DOX. Apoptosis assay showed that DOX-loaded conjugates decreased the cell viability from 81.87 ± 5.94% to 54.83 ± 3.63% (DOX concentration 2 μg/ml). At 48 h, more accumulation and distribution in the nuclei were observed after treatment with DOX-loaded conjugates.
  
  
  CONCLUSIONS
  PF127-PAMAM conjugates showed superiority in the treatment of MCF-7/ADR, which implied the potential vehicles of anticancer drugs for the reversal of MDR.
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Han
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Gao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000008:administration & dosage / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D061986:MCF-7 Cells; D008823:Micelles; D020442:Poloxamer / Q000737:chemistry; D011817:Rabbits
chemical_list: D000970:Antineoplastic Agents; D050091:Dendrimers; D004337:Drug Carriers; D008823:Micelles; D020442:Poloxamer; D004317:Doxorubicin
keywords: PAMAM dendrimer; doxorubicin; drug resistance; pluronic; unimolecular micelle