PEG branched polymer for functionalization of nanomaterials with ultralong blood circulation.
Nanomaterials have been actively pursued for biological and medical applications in recent years. Here, we report the synthesis of several new poly(ethylene glycol) grafted branched polymers for functionalization of various nanomaterials including carbon nanotubes, gold nanoparticles (NPs), and gold nanorods (NRs), affording high aqueous solubility and stability for these materials. We synthesize different surfactant polymers based upon poly(gamma-glutamic acid) (gammaPGA) and poly(maleic anhydride-alt-1-octadecene) (PMHC18). We use the abundant free carboxylic acid groups of gammaPGA for attaching lipophilic species such as pyrene or phospholipid, which bind to nanomaterials via robust physisorption. Additionally, the remaining carboxylic acids on gammaPGA or the amine-reactive anhydrides of PMHC18 are then PEGylated, providing extended hydrophilic groups, affording polymeric amphiphiles. We show that single-walled carbon nanotubes (SWNTs), Au NPs, and NRs functionalized by the polymers exhibit high stability in aqueous solutions at different pH values, at elevated temperatures, and in serum. Moreover, the polymer-coated SWNTs exhibit remarkably long blood circulation (t(1/2) = 22.1 h) upon intravenous injection into mice, far exceeding the previous record of 5.4 h. The ultralong blood circulation time suggests greatly delayed clearance of nanomaterials by the reticuloendothelial system (RES) of mice, a highly desired property for in vivo applications of nanomaterials, including imaging and drug delivery.
Prencipe
Giuseppe
G
Department of Chemistry, Stanford University, Keck Science Building, Rm 125, 380 Roth Way, Stanford, California 94305, USA.
Tabakman
Scott M
SM
Welsher
Kevin
K
Liu
Zhuang
Z
Goodwin
Andrew P
AP
Zhang
Li
L
Henry
Joy
J
Dai
Hongjie
H
D000818:Animals; D001776:Blood Circulation Time; D002244:Carbon / Q000737:chemistry*; D006046:Gold / Q000737:chemistry*; D051379:Mice; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D012995:Solubility
D011092:Polyethylene Glycols; D002244:Carbon; D006046:Gold