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

Schuster, Benjamin S.; Allan, Daniel B.; Kays, Joshua C.; Hanes, Justin; Leheny, Robert L.

doi:10.1016/j.jconrel.2017.05.035

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

Journal Article · Wed May 31 00:00:00 EDT 2017 · Journal of Controlled Release

DOI:https://doi.org/10.1016/j.jconrel.2017.05.035· OSTI ID:1434764

Schuster, Benjamin S. ^[1]; Allan, Daniel B. ^[2]; Kays, Joshua C. ^[3]; Hanes, Justin ^[3]; Leheny, Robert L. ^[4]

Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States); Univ. of Pennsylvania, Philadelphia, PA (United States)
Johns Hopkins Univ., Baltimore, MD (United States); Brookhaven National Lab. (BNL), Upton, NY (United States)
Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States)
Johns Hopkins Univ., Baltimore, MD (United States)

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 and 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.

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Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: SC0012704

OSTI ID:: 1434764

Report Number(s):: BNL-203478-2018-JAAM

Journal Information:: Journal of Controlled Release, Vol. 260, Issue C; ISSN 0168-3659

Publisher:: Controlled Release SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 10 works

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36 MATERIALS SCIENCE
Photoactivation
Fibrin
Cystic fibrosis
Nanoparticle
Drug delivery
Particle tracking
FRAP
Fluorescence microscopy
Diffusion

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