Elucidating the Mechanism of Silica Nanoparticle PEGylation

Feb 8, 2016 - Katharine W. Oleske , Katherine P. Barteau , Melik Ziya Turker , Peter A. Beaucage , Lara A. Estroff , and Ulrich Wiesner. Macromolecule...
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Article

Elucidating the mechanism of silica nanoparticle PEGylation processes using fluorescence correlation spectroscopies Kai Ma, Duhan Zhang, Ying Cong, and Ulrich Wiesner Chem. Mater., Just Accepted Manuscript • DOI: 10.1021/acs.chemmater.6b00030 • Publication Date (Web): 08 Feb 2016 Downloaded from http://pubs.acs.org on February 22, 2016

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Chemistry of Materials

Elucidating the mechanism of silica nanoparticle PEGylation processes using fluorescence correlation spectroscopies Kai Ma, Duhan Zhang, Ying Cong, Ulrich Wiesner*  Department of Materials Science and Engineering, Cornell University, Ithaca, New York 14850, United States           ABSTRACT: Surface modification with polyethylene glycol (PEG; PEGylation) is a widely used technique to improve nano‐ particle (NP) stability, biocompatibility and biodistribution profiles. In particular, PEGylation of silica surfaces and coatings  plays a pivotal role across various classes of NPs. Despite the use of numerous protocols there is limited fundamental un‐ derstanding of the mechanisms of these processes for NPs. Here, after reaction optimization for particle stability, we employ  fluorescence correlation and cross‐correlation spectroscopy (FCS, FCCS) on ultrasmall (170 bil‐ lion in 2019.1 As one of the most promising nanomedicine  candidates, multifunctional organic‐inorganic hybrid NPs  have  attracted  significant  research  attention  world‐wide  for both imaging/diagnostics and therapeutics.2‐5 However,  in order to successfully translate hybrid NPs from the la‐ boratory to the clinic, PEGylation is an essential step to en‐ dow NPs with long‐term stability as well as favorable bio‐ distribution and pharmacokinetics (PK) profiles.6‐8 In the  last  decade,  silica  coating  techniques  have  been  estab‐ lished to stabilize inorganic NPs in aqueous media without  disturbing  their  physical  properties.9  Therefore  the  PEGylation  of  silica  surfaces  and  coatings  plays  a  pivotal  role  for  nanomedicine  applications  across  various  classes  of nanomaterials, including dense10 and mesoporous silica  nanoparticles (SNPs),11,12 quantum dots,13 gold NPs,14,15 mag‐ netic NPs,16 graphene,17 and carbon nanotubes.18    Compared to the well‐studied PEGylation of pharmaceuti‐ cals,19 e.g. proteins and peptides, the PEGylation of NPs en‐ abling  desirable  biodistribution  and  PK  often  remains  challenging due to the complexity of the interfacial reac‐ tions  between  NP  surfaces  and  ligand  molecules.20,21  De‐ spite  the  use  of  numerous  protocols  to  PEGylate  specific  NPs,22 little is known mechanistically about how this pro‐ cess  proceeds,  which  in  turn  hampers  the  production  of  clinically translatable nanomaterials. To that end, here we 

take  advantage  of  highly‐tunable  silica  sol‐gel  chemistry  and use ultrasmall (