Critical parameters in the pegylation of gold nanoshells for biomedical applications: Anin vitromacrophage study

James Chen Yong Kaha, Ker Yi Wonga, Koon Gee Neohb, Jie Han Songc, Jason Wei Ping Fuc, Subodh Mhaisalkarc, Malini Olivo & Colin James Richard Sheppard*aa Division of Bioengineering, National University of Singapore, 7 Engineering Drive 1Singapore, 117574, Singaporeb Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4Singapore, 117576, Singaporec School of Materials Science and Engineering, Nanyang Technological University, Block N4.1, Nanyang AvenueSingapore, 639798, Singapored Division of Medical Sciences, National Cancer Centre Singapore, 11 Hospital DriveSingapore, 169610, Singaporee Singapore Bioimaging Consortium, Biomedical Sciences Institutes, 11 Biopolis Way, #02-02 HeliosSingapore, 138667, Singaporef Department of Pharmacy, National University of Singapore, Block S4, 18 Science Drive 4Singapore, 117543, SingaporeAddress for Correspondence: C. J. R. Sheppard, Division of Bioengineering, National University of Singapore, Block E3A #04-15, 7 Engineering Drive 1, Singapore, 117576, Singapore, 65 65161910. E-mail: colin@nus.edu.sgPegylation of gold nanoshells provides an effective means to reduce their reticuloendothelial system (RES) clearance in body. In this study, we perform a parametric investigation on the factors that would affect the macrophage uptake of gold nanoshells with the aim to optimize their pegylation and minimize their macrophage uptake. We synthesized and pegylated the gold nanoshells using methoxy-poly(ethylene glycol)-thiol and employed an in vitro macrophage assay to examine the effect of surface density of poly(ethylene glycol) (PEG), chain length of the PEG, and size of the gold nanoshells on their macrophage uptake. We have shown that a saturated surface density would minimize macrophage uptake, which could be obtained by experimental titration-based Ellman’s reagent. Our results suggest that the chain length of PEG and size of gold nanoshells influence the surface density of PEG. We have also shown that PEG with molecular weight of around 2000 Da and a size range larger than 186 nm would be appropriate for facilitating a high surface density. Our in vitro macrophage system thus provides a good model to accurately predict the RES response to different pegylation parameters.