title: Design and potential application of PEGylated gold nanoparticles with size-dependent permeation through brain microvasculature.
abstract: Gold nanoparticles (AuNPs) have gained prominence in several targeting applications involving systemic cancers. Their enhanced permeation and retention within permissive tumor microvasculature provides a selective advantage for targeting. Malignant brain tumors also exhibit transport-permissive microvasculature secondary to blood-brain barrier disruption. Hence AuNPs may have potential relevance for brain tumor targeting. However, there are currently no studies that systematically examine brain microvasculature permeation of polyethylene glycol (PEG)-functionalized AuNPs. Such studies could pave the way for rationale AuNP design for passive targeting of malignant tumors. In this report we designed and characterized AuNPs with varying core particle sizes (4-24 nm) and PEG chain lengths [molecular weight 1000-10,000]. Using an in-vitro model designed to mimic the transport-permissive brain microvasculature, we demonstrate size-dependent permeation properties with respect to core particle size and PEG chain length. In general short PEG chain length (molecular weight 1000-2000) in combination with smallest core size led to optimum permeation in our model system.
  
  
  BACKGROUND
  In this report the authors designed and characterized PEGylated gold NPs with varying core particle sizes and PEG chain lengths and demonstrate that short PEG chain length in combination with smallest core size led to optimum permeation of a blood-brain barrier model system. These findings may pave the way to optimized therapy of malignant brain tumors.
authors: The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors: Arnold B
authors: AB
authors: Etame
authors: Christian A
authors: CA
authors: Smith
authors: Warren C W
authors: WC
authors: Chan
authors: James T
authors: JT
authors: Rutka