skip to main content

DOE PAGESDOE PAGES

This content will become publicly available on May 31, 2018

Title: Photoactivatable fluorescent probes reveal heterogeneous nanoparticle permeation through biological gels at multiple scales

Diffusion through biological gels is crucial for effective drug delivery using nanoparticles. Here, we demonstrate a new method to measure diffusivity over a large range of length scales – from tens of nanometers to tens of micrometers – using photoactivatable fluorescent nanoparticle probes. We have applied this method to investigate the length-scale dependent mobility of nanoparticles in fibrin gels and in sputum from patients with cystic fibrosis (CF). Nanoparticles composed of poly(lactic-co-glycolic acid), with polyethylene glycol coatings to resist bioadhesion, were internally labeled with caged rhodamine to make the particles photoactivatable. We activated particles within a region of sample using brief, targeted exposure to UV light, uncaging the rhodamine and causing the particles in that region to become fluorescent. We imaged the subsequent spatiotemporal evolution in fluorescence intensity and observed the collective particle diffusion over tens of minutes and tens of micrometers. We also performed complementary multiple particle tracking experiments on the same particles, extending significantly the range over which particle motion and its heterogeneity can be observed. In fibrin gels, both methods showed an immobile fraction of particles and a mobile fraction that diffused over all measured length scales. In the CF sputum, particle diffusion was spatially heterogeneous andmore » locally anisotropic but nevertheless typically led to unbounded transport extending tens of micrometers within tens of minutes. Lastly, these findings provide insight into the mesoscale architecture of these gels and its role in setting their permeability on physiologically relevant length scales, pointing toward strategies for improving nanoparticle drug delivery.« less
Authors:
 [1] ;  [2] ;  [3] ;  [3] ;  [4]
  1. Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States); Univ. of Pennsylvania, Philadelphia, PA (United States)
  2. Johns Hopkins Univ., Baltimore, MD (United States); Brookhaven National Lab. (BNL), Upton, NY (United States)
  3. Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States)
  4. Johns Hopkins Univ., Baltimore, MD (United States)
Publication Date:
Report Number(s):
BNL-203478-2018-JAAM
Journal ID: ISSN 0168-3659
Grant/Contract Number:
SC0012704
Type:
Accepted Manuscript
Journal Name:
Journal of Controlled Release
Additional Journal Information:
Journal Volume: 260; Journal Issue: C; Journal ID: ISSN 0168-3659
Publisher:
Controlled Release Society
Research Org:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; Photoactivation; Fibrin; Cystic fibrosis; Nanoparticle; Drug delivery; Particle tracking; FRAP; Fluorescence microscopy; Diffusion
OSTI Identifier:
1434764