title: Pluronic-attached polyamidoamine dendrimer conjugates overcome drug resistance in breast cancer.
abstract: OBJECTIVE
  To design pluronic F68 (PF68)-conjugated polyamidoamine (PAMAM) dendrimer conjugates for doxorubicin (DOX) delivery for overcoming multidrug resistance, and clarify the reversal mechanism.
  
  
  METHODS
  A series of PAMAM-PF68 conjugates were designed. The antitumor activity of the DOX-loaded conjugates was evaluated against MCF-7/ADR cells, tumor spheroids and tumors. Several bioinformatics were detected to characterize the reversal mechanism.
  
  
  RESULTS
  Increased antitumor activity of the DOX-loaded conjugates was achieved in vitro and in vivo. The complexes induced more DOX accumulation via caveolae-mediated endocytosis. After escaping from the endosome/lysosome, the nuclear trafficking of DOX was achieved. Apoptosis was significantly increased by regulating mitochondrial function and gene expression.
  
  
  CONCLUSIONS
  With optimized PF68 modification, PAMAM-PF68 conjugates can significantly overcome multidrug resistance in vitro and in vivo.
authors: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China.
authors: Meng
authors: M
authors: Wang
authors: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China.
authors: Ying
authors: Y
authors: Li
authors: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China.
authors: Mingyi
authors: M
authors: HuangFu
authors: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China.
authors: Yi
authors: Y
authors: Xiao
authors: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China.
authors: Tianyuan
authors: T
authors: Zhang
authors: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China.
authors: Min
authors: M
authors: Han
authors: Department of Pharmacy, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, PR China.
authors: Donghang
authors: D
authors: Xu
authors: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China.
authors: Fangyuan
authors: F
authors: Li
authors: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China.
authors: Daishun
authors: D
authors: Ling
authors: National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330006, PR China.
authors: Yi
authors: Y
authors: Jin
authors: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China.
authors: Jianqing
authors: J
authors: Gao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D050091:Dendrimers / Q000008:administration & dosage / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D011073:Polyamines / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D050091:Dendrimers; C531249:Poly(amidoamine); D011073:Polyamines; D004317:Doxorubicin
keywords: PAMAM dendrimer; cancer treatment; drug resistance; mechanism; pluronic