title: pH-Activated Targeting Drug Delivery System Based on the Selective Binding of Phenylboronic Acid.
abstract: Phenylboronic acid (PBA) is a tumor-targeting molecule, but its nonspecific interaction with normal cells or other components containing cis-diol residues undoubtedly limits its potential application in tumor-targeting drug delivery. Herein, we developed fructose-coated mixed micelles via PBA-terminated polyethylene glycol monostearate (PBA-PEG-C18) and Pluronic P123 (PEG20-PPG70-PEG20) to solve this problem, as the stability of borate formed by PBA and fructose was dramatically dependent on pH. The fluorescence spectroscopic results indicated that the borate formed by PBA and fructose decomposed at a decreased pH, and better binding between PBA and sialic acid (SA) was observed at a low pH. These results implied that the fructose groups decorated on the surface of the micelles could be out-competed by SA at a low pH. In vitro uptake and cytotoxicity studies demonstrated that the fructose coating on the mixed micelles improved the endocytosis and enhanced the cytotoxicity of drug-loaded mixed micelles in HepG2 cells but reduced the cytotoxicity in normal cells. These results demonstrate that a simple decorating strategy may facilitate PBA-targeted nanoparticles for tumor-specific drug delivery.
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education and College of Chemistry and Molecular Science, Wuhan University , Wuhan 430072, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education and College of Chemistry and Molecular Science, Wuhan University , Wuhan 430072, China.
authors.forename: Jia-Qi
authors.initials: JQ
authors.lastname: Xu
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education and College of Chemistry and Molecular Science, Wuhan University , Wuhan 430072, China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Yi
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education and College of Chemistry and Molecular Science, Wuhan University , Wuhan 430072, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education and College of Chemistry and Molecular Science, Wuhan University , Wuhan 430072, China.
authors.forename: Si-Xue
authors.initials: SX
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education and College of Chemistry and Molecular Science, Wuhan University , Wuhan 430072, China.
authors.forename: Ren-Xi
authors.initials: RX
authors.lastname: Zhuo
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education and College of Chemistry and Molecular Science, Wuhan University , Wuhan 430072, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D001897:Boronic Acids / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy; D011092:Polyethylene Glycols
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D008823:Micelles; D011092:Polyethylene Glycols; C010686:benzeneboronic acid
keywords: competitive binding; drug delivery; pH activation; phenylboronic acid; target