Preparation of Poly(ethylene glycol) Protected Nanoparticles with Variable Bioconjugate Ligand Density

被引:99
作者
Gindy, Marian E. [1 ]
Ji, Shengxiang [3 ]
Hoye, Thomas R. [3 ]
Panagiotopoulos, Athanassios Z. [1 ,2 ]
Prud'homme, Robert K. [1 ]
机构
[1] Princeton Univ, Dept Chem Engn, Princeton, NJ 08544 USA
[2] Princeton Univ, Princeton Inst Sci & Technol Mat, Princeton, NJ 08544 USA
[3] Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USA
基金
美国国家科学基金会;
关键词
D O I
10.1021/bm8002013
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Maleimide-functional poly(ethylene glycol)-b-poly(epsilon-caprolactone) nanoparticles (NPs) were prepared via the Flash NanoPrecipitation technique. Subsequent reaction with a model ligand, bovine serum albumin (BSA), was conducted using thiol-maleimide conjugation. Reaction of up to 22% of NP surface maleimide-PEG tethers was obtained, with the percent conversion being essentially independent of the ratio of maleimide-PEG to methyl-PEG over the range 30-100%, respectively. At the highest surface coverage, BSA is calculated to essentially cover the NP surface area. Reaction parameters (reaction order and docking constant) describing the extent of ligand conjugation were determined. The reaction order is applicable to the conjugation of ligands presenting free thiol functionalities, while the value of the docking constant is ligand-dependent and accounts for physical and dynamic properties of the ligand-PEG interaction. Jointly, the particle formation process, using block copolymer-directed kinetically controlled assembly and surface functionalization represent a versatile new platform for the preparation of bioconjugated NPs with accurate control of ligand density and minimal processing steps.
引用
收藏
页码:2705 / 2711
页数:7
相关论文
共 48 条
[11]  
Duncan R, 1998, ANN ONCOL, V9, P39
[12]   Polymer conjugates as anticancer nanomedicines [J].
Duncan, Ruth .
NATURE REVIEWS CANCER, 2006, 6 (09) :688-701
[13]   TISSUE SULFHYDRYL GROUPS [J].
ELLMAN, GL .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1959, 82 (01) :70-77
[14]   Studies on protein-liposome coupling using novel thiol-reactive coupling lipids: Influence of spacer length and polarity [J].
Fleiner, M ;
Benzinger, P ;
Fichert, T ;
Massing, U .
BIOCONJUGATE CHEMISTRY, 2001, 12 (04) :470-475
[15]   Composite block copolymer stabilized nanoparticles: Simultaneous encapsulation of organic actives and inorganic nanostructures [J].
Gindy, Marian E. ;
Panagiotopoulos, Athanassios Z. ;
Prud'homme, Robert K. .
LANGMUIR, 2008, 24 (01) :83-90
[16]  
JANATOVA J, 1968, J BIOL CHEM, V243, P3612
[17]  
JI S, 2006, THESIS U MINNESOTA M
[18]   Flash NanoPrecipitation of organic actives and block copolymers using a confined impinging jets mixer [J].
Johnson, BK ;
Prud'homme, RK .
AUSTRALIAN JOURNAL OF CHEMISTRY, 2003, 56 (10) :1021-1024
[19]  
JOHNSON BK, 2003, PHYS REV LETT, V56
[20]   A NEW CLASS OF DRUG CARRIERS - MICELLES OF POLY(OXYETHYLENE)-POLY(OXYPROPYLENE) BLOCK COPOLYMERS AS MICROCONTAINERS FOR DRUG TARGETING FROM BLOOD IN BRAIN [J].
KABANOV, AV ;
BATRAKOVA, EV ;
MELIKNUBAROV, NS ;
FEDOSEEV, NA ;
DORODNICH, TY ;
ALAKHOV, VY ;
CHEKHONIN, VP ;
NAZAROVA, IR ;
KABANOV, VA .
JOURNAL OF CONTROLLED RELEASE, 1992, 22 (02) :141-157