title: d-Fructose Modification Enhanced Internalization of Mixed Micelles in Breast Cancer Cells via GLUT5 Transporters.
abstract: d-Fructose modified poly(ε-caprolactone)-polyethylene glycol (PCL-PEG-Fru) diblock amphiphile is synthesized via Cu(I)-catalyzed click chemistry, which self-assembles with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) into PCL-PEG-Fru/TPGS mixed micelles (PPF MM). It has been proven that glucose transporter (GLUT)5 is overexpressed in MCF-7 cells other than L929 cells. In this study, PPF MM exhibit a significantly higher uptake efficiency than fructose-free PCL-PEG-N3/TPGS mixed micelles in both 2D MCF-7 cells and 3D tumor spheroids. Also, the presence of free d-fructose competitively inhibits the internalization of PPF MM in MCF-7 cells other than L929 cells. PPF MM show selective tumor accumulation in MCF-7 breast tumor bearing mice xenografts. Taken together, PPF MM represent a promising nanoscale carrier system to achieve GLUT5-mediated cell specific delivery in cancer therapy.
authors.affiliation: Key Laboratory of Drug Targeting and Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Drug Targeting and Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
authors.forename: Xianyan
authors.initials: X
authors.lastname: Qin
authors.affiliation: Key Laboratory of Drug Targeting and Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.affiliation: Key Laboratory of Drug Targeting and Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Fu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D005632:Fructose / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051296:Glucose Transporter Type 5 / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D009363:Neoplasm Proteins / Q000378:metabolism*; D011091:Polyesters / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; D051296:Glucose Transporter Type 5; D008823:Micelles; D009363:Neoplasm Proteins; D011091:Polyesters; C495726:SLC2A5 protein, human; C016240:polycaprolactone; D005632:Fructose; D011092:Polyethylene Glycols
keywords: GLUT5; d-fructose; mixed micelles; poly(ε-caprolactone); self-assembly