Blood-nanoparticle interactions and in Vivo biodistribution: Impact of surface peg and ligand properties

Neha B. Shah, Gregory M Vercellotti, James G. White, Adrian Fegan, Carston R Wagner, John C Bischof

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Theranostic nanoparticles (NPs) cannot reach their target tissue without first passing through blood; however, the influence of blood protein and blood cell interactions on NP biodistribution are not well understood. The current work shows that 30 nm PEGylated gold NPs (GNPs) interact not only with blood proteins as thought before but also with blood cells (especially platelets and monocytes) in vivo and that longer blood circulation correlates strongly with tumor uptake. Further, GNP surface properties such as negative charge or lyophilization had either a minimal (i.e., charge) or 15-fold increase (i.e., fresh vs lyophilized) in blood retention times and tumor uptake. Tumor accumulation was increased over 10-fold by use of a bioactive ligand (i.e., TNF) on the lyophilized GNP surface. Resident macrophages were primarily responsible for the bulk of GNP uptake in liver while spleen uptake was highly surface property dependent and appears to involve macrophages and cellular interaction between the red and white pulp. This study shows that the PEG layer and ligand on the surface of the NP are critical to blood interactions and eventual tumor and RES organ biodistribution in vivo.

Original languageEnglish (US)
Pages (from-to)2146-2155
Number of pages10
JournalMolecular pharmaceutics
Volume9
Issue number8
DOIs
StatePublished - Aug 6 2012

Fingerprint

Gold
Nanoparticles
Ligands
Surface Properties
Blood Proteins
Blood Cells
Neoplasms
Macrophages
Freeze Drying
Blood Circulation
Cell Communication
Monocytes
Blood Platelets
Spleen
Liver

Keywords

  • PEGylation
  • biodistribution
  • blood?particle interactions
  • gold nanoparticles
  • ligand
  • lyophilization

Cite this

Blood-nanoparticle interactions and in Vivo biodistribution : Impact of surface peg and ligand properties. / Shah, Neha B.; Vercellotti, Gregory M; White, James G.; Fegan, Adrian; Wagner, Carston R; Bischof, John C.

In: Molecular pharmaceutics, Vol. 9, No. 8, 06.08.2012, p. 2146-2155.

Research output: Contribution to journalArticle

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