PEG Branched Polymer for Functionalization of Nanomaterials with Ultralong Blood Circulation

TL;DR

This paper reports the synthesis of PEG-branched polymers for nanomaterial functionalization, achieving ultralong blood circulation times in mice, which enhances their potential for biomedical imaging and drug delivery.

Contribution

The study introduces new PEG-grafted branched-polymers that significantly improve nanomaterials' stability and circulation time in vivo, surpassing previous benchmarks.

Findings

Nanomaterials functionalized with these polymers show high stability in various conditions.

SWNTs exhibit a blood half-life of 22.1 hours, much longer than previous records.

Polymer-coated nanomaterials demonstrate delayed clearance by the immune system.

Abstract

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 (NP) and gold nanorods (NRs), affording high aqueous solubility and stability for these materials. We synthesize different surfactant polymers based upon poly-(g-glutamic acid) (gPGA) and poly(maleic anhydride-alt-1-octadecene) (PMHC18). We use the abundant free carboxylic acid groups of gPGA for attaching lipophilic species such as pyrene or phospholipid, which bind to nanomaterials via robust physisorption. Additionally, the remaining carboxylic acids on gPGA 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 pHs, at elevated temperatures and in serum. Morever, the polymer-coated SWNTs exhibit remarkably long blood circulation (t1/2 22.1 h) upon intravenous injection into mice, far exceeding the previous record of 5.4 h. The ultra-long 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.