Format

Send to

Choose Destination
Nanomedicine. 2017 May;13(4):1495-1506. doi: 10.1016/j.nano.2016.12.019. Epub 2017 Jan 5.

Mechanisms that determine nanocarrier targeting to healthy versus inflamed lung regions.

Author information

1
Pulmonary and Critical Care Division, University of Pennsylvania, Philadelphia, PA, USA; Department of Pharmacology and Center for Translational Targeted Therapeutics and Nanomedicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
2
Department of Pharmacology and Center for Translational Targeted Therapeutics and Nanomedicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
3
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
4
Department of Respiratory Medicine, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
5
Pulmonary and Critical Care Division, University of Pennsylvania, Philadelphia, PA, USA.
6
Department of Pharmacology and Center for Translational Targeted Therapeutics and Nanomedicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: muzykant@mail.med.upenn.edu.

Abstract

Inflamed organs display marked spatial heterogeneity of inflammation, with patches of inflamed tissue adjacent to healthy tissue. To investigate how nanocarriers (NCs) distribute between such patches, we created a mouse model that recapitulates the spatial heterogeneity of the inflammatory lung disease ARDS. NCs targeting the epitope PECAM strongly accumulated in the lungs, but were shunted away from inflamed lung regions due to hypoxic vasoconstriction (HVC). In contrast, ICAM-targeted NCs, which had lower whole-lung uptake than PECAM/NCs in inflamed lungs, displayed markedly higher NC levels in inflamed regions than PECAM/NCs, due to increased regional ICAM. Regional HVC, epitope expression, and capillary leak were sufficient to predict intra-organ of distribution of NCs, antibodies, and drugs. Importantly, these effects were not observable with traditional spatially-uniform models of ARDS, nor when examining only whole-organ uptake. This study underscores how examining NCs' intra-organ distribution in spatially heterogeneous animal models can guide rational NC design.

KEYWORDS:

ARDS; Inflammation; Nano-bio interface; Nanocarriers; Nanoparticle biological interactions; Nanoparticles; Patchy; Spatial heterogeneity; Whole organ distribution

PMID:
28065731
PMCID:
PMC5518469
DOI:
10.1016/j.nano.2016.12.019
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center