Probing of the assembly structure and dynamics within nanoparticles during interaction with blood proteins

Yuanpei Li, Madhu S. Budamagunta, Juntao T Luo, Wenwu Xiao, John C. Voss, Kit S. Lam

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Fully understanding the influence of blood proteins on the assembly structure and dynamics within nanoparticles is difficult because of the complexity of the system and the difficulty in probing the diverse elements and milieus involved. Here we show the use of site-specific labeling with spin probes and fluorophores combined with electron paramagnetic resonance (EPR) spectroscopy and fluorescence resonance energy transfer (FRET) measurements to provide insights into the molecular architecture and dynamics within nanoparticles. These tools are especially useful for determining nanoparticle stability in the context of blood proteins and lipoproteins and have allowed us to quantitatively analyze the dynamic changes in assembly structure, local stability, and cargo diffusion of a class of novel telodendrimer-based micellar nanoparticles. When combined with human plasma and individual plasma components, we find that non-cross-linked nanoparticles immediately lose their original assembly structure and release their payload upon interaction with lipoproteins. In contrast, serum albumins and immunoglobulin gamma have moderate affects on the integrity of the nanoparticles. Disulfide cross-linked nanoparticles show minimal interaction with lipoproteins and can better retain their assembly structure and payload in vitro and in vivo. We further demonstrate how the enhanced stability and release property of disulfide cross-linked nanoparticles can be reversed in reductive conditions. These findings identify factors that are crucial to the performance of nanomedicines and provide design modes to control their interplay with blood factors.

Original languageEnglish (US)
Pages (from-to)9485-9495
Number of pages11
JournalACS Nano
Volume6
Issue number11
DOIs
StatePublished - Nov 27 2012

Keywords

  • drug delivery
  • EPR
  • FRET
  • lipoprotein particle
  • micellar nanoparticle
  • protein-nanoparticle interaction
  • site-specific labeling
  • structure and dynamics

ASJC Scopus subject areas

  • Engineering(all)
  • Materials Science(all)
  • Physics and Astronomy(all)

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