title: Polymeric micelles with α-glutamyl-terminated PEG shells show low non-specific protein adsorption and a prolonged in vivo circulation time.
abstract: Although PEG remains the gold standard for stealth functionalization in drug delivery field up to date, complete inhibition of protein corona formation on PEG-coated nanoparticles remains a challenge. To improve the stealth property of PEG, herein an α-glutamyl group was conjugated to the end of PEG and polymeric micelles with α-glutamyl-terminated PEG shells were prepared. After incubation with bovine serum albumin or in fetal calf serum, the size of the micelles changed slightly, while the size of the micelles of similar diblock copolymer but without α-glutamyl group increased markedly. These results indicated that the micelles with α-glutamyl-terminated PEG shells showed low non-specific protein adsorption. In vivo blood clearance kinetics assay showed that the micelles with α-glutamyl-terminated PEG shells exhibited a longer in vivo blood circulation time compared with similar micelles but without α-glutamyl groups. The better stealth property of the micelles with α-glutamyl-terminated PEG shells was presumably attributed to the zwitterionic property of the α-glutamyl groups.
authors.affiliation: Key Laboratory of Functional Polymer Materials (Ministry of Education) and Institute of Polymer Chemistry, Nankai University, Tianjin 300071, China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, China.
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, and Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, and Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
authors.forename: Chenhong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Key Laboratory of Functional Polymer Materials (Ministry of Education) and Institute of Polymer Chemistry, Nankai University, Tianjin 300071, China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, China.
authors.forename: Leijia
authors.initials: L
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, and Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
authors.forename: Tianhong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, and Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Functional Polymer Materials (Ministry of Education) and Institute of Polymer Chemistry, Nankai University, Tianjin 300071, China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, China. Electronic address: yanhs@nankai.edu.cn.
authors.forename: Husheng
authors.initials: H
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, and Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China. Electronic address: keliangliu55@126.com.
authors.forename: Keliang
authors.initials: K
authors.lastname: Liu
mesh_terms: D000327:Adsorption; D000818:Animals; D002417:Cattle; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000737:chemistry
chemical_list: D020099:Coated Materials, Biocompatible; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; C000595209:polyethylene glycol 1000
keywords: Drug delivery; Polymeric micelles; Stealth; Zwitterionic; α-Glutamyl