The effect of ligand composition on the in vivo fate of multidentate poly(ethylene glycol) modified gold nanoparticles.
Multidentate ligands are expected to improve the performance of inorganic nanoparticles (NPs) in biological application. Designing robust multidentate ligands by a facile way and understanding the impact of ligand composition on NP's property are greatly important. We report the effective synthesis of hydrophilic copolymers containing pendent thiol groups along a polyethylene glycol (PEG) methacrylate backbone by classical free radical copolymerization. Gold nanoparticles (AuNPs) coated by these multidentate ligands with two different ratios of thiols to PEG segment (≈ 1:1 and 1:2) showed much higher colloidal stability in the presence of dithiothreitol (DTT) than AuNPs coated by monothiol-anchored PEG, and AuNPs coated by ligands with higher fraction of thiol groups showed slightly better resistance to DTT competition than did AuNPs coated by ligands with lower thiol fraction, but both of them exhibited excellent stabilities in biological media without obvious difference. In vitro study of uptake by macrophages did not showed significant difference between the two AuNPs with very low endocytosis. However, AuNPs coated by ligands with higher PEG content were found to accumulate in liver with a significantly lower level but a higher level in spleen than AuNPs coated by ligands with lower PEG contents. Moreover, the AuNPs coated with by ligands with higher PEG content showed higher tumor uptake. Additionally, AuNPs coated with both ligands demonstrated good biocompatibility as evaluated by cytotoxicity assays and histological analysis. Together, the composition of multidentate ligands will not only affect the stability of NPs under extreme conditions but also result in quite different fate of NPs in vivo, which can be tailored case by case.
MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
Xiangsheng
X
Liu
Nan
N
Huang
Haibo
H
Wang
Huan
H
Li
Qiao
Q
Jin
Jian
J
Ji
D000818:Animals; D002460:Cell Line; D006046:Gold / Q000737:chemistry*; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry*; D008689:Methacrylates / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols / Q000737:chemistry*; D013154:Spleen / Q000378:metabolism
D008689:Methacrylates; C524499:polyethylene glycol methacrylate; D011092:Polyethylene Glycols; D006046:Gold
Biocompatibility; Biodistribution; Gold nanoparticles; Ligand composition; Multidentate poly(ethylene glycol); Stability