Neutrophil-Mediated Delivery of Therapeutic Nanoparticles across Blood Vessel Barrier for Treatment of Inflammation and Infection

Dafeng Chu; Jin Gao; Zhenjia Wang

doi:10.1021/acsnano.5b05583

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Neutrophil-Mediated Delivery of Therapeutic Nanoparticles across Blood Vessel Barrier for Treatment of Inflammation and Infection

Journal article

Open access

Peer reviewed

Neutrophil-Mediated Delivery of Therapeutic Nanoparticles across Blood Vessel Barrier for Treatment of Inflammation and Infection

Dafeng Chu, Jin Gao and Zhenjia Wang

ACS nano, Vol.9(12), pp.11800-11811

12/22/2015

DOI: https://doi.org/10.1021/acsnano.5b05583

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https://hdl.handle.net/2376/116777

PMCID: PMC4699556

PMID: 26516654

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https://doi.org/10.1021/acsnano.5b05583View

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Abstract

Neutrophils - chemistry

Drug Carriers - therapeutic use

Nanoparticles - chemistry

Infection - drug therapy

Blood Vessels - metabolism

Cells, Cultured

Male

Drug Carriers - chemistry

Serum Albumin, Bovine - pharmacokinetics

Animals

Inflammation - drug therapy

Anti-Bacterial Agents - chemistry

Anti-Bacterial Agents - pharmacokinetics

Serum Albumin, Bovine - chemistry

Drug Carriers - pharmacokinetics

Mice

Neutrophils - metabolism

Endothelial cells form a monolayer in lumen of blood vessels presenting a great barrier for delivery of therapeutic nanoparticles (NPs) into extravascular tissues where most diseases occur, such as inflammation disorders and infection. Here, we report a strategy for delivering therapeutic NPs across this blood vessel barrier by nanoparticle in situ hitchhiking activated neutrophils. Using intravital microscopy of TNF-α-induced inflammation of mouse cremaster venules and a mouse model of acute lung inflammation, we demonstrated that intravenously (iv) infused NPs made from denatured bovine serum albumin (BSA) were specifically internalized by activated neutrophils, and subsequently, the neutrophils containing NPs migrated across blood vessels into inflammatory tissues. When neutrophils were depleted using anti-Gr-1 in a mouse, the transport of albumin NPs across blood vessel walls was robustly abolished. Furthermore, it was found that albumin nanoparticle internalization did not affect neutrophil mobility and functions. Administration of drug-loaded albumin NPs markedly mitigated the lung inflammation induced by LPS (lipopolysaccharide) or infection by Pseudomonas aeruginosa. These results demonstrate the use of an albumin nanoparticle platform for in situ targeting of activated neutrophils for delivery of therapeutics across the blood vessel barriers into diseased sites. This study demonstrates our ability to hijack neutrophils to deliver nanoparticles to targeted diseased sites.

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Title: Neutrophil-Mediated Delivery of Therapeutic Nanoparticles across Blood Vessel Barrier for Treatment of Inflammation and Infection
Creators: Dafeng Chu - Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University , Spokane, Washington 99210, United States
Jin Gao - Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University , Spokane, Washington 99210, United States
Zhenjia Wang - Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University , Spokane, Washington 99210, United States
Publication Details: ACS nano, Vol.9(12), pp.11800-11811
Academic Unit: Pharmaceutical Sciences, Department of
Publisher: United States
Grant note: K25 HL111157 / NHLBI NIH HHS K25HL111157 / NHLBI NIH HHS
Identifiers: 99900547972201842
Language: English
Resource Type: Journal article