DataVXACS NanoPaper
journal article·2023-07-25Open access

Targeted Nanocarriers Co-Opting Pulmonary Intravascular Leukocytes for Drug Delivery to the Injured Brain

Jia Nong, Patrick M. Glassman, Jacob W. Myerson, Viviana Zuluaga-Ramirez, Alba Rodriguez-Garcia, Alvin Mukalel, Serena Omo-Lamai, Landis R. Walsh, Marco E. Zamora, Xijing Gong, Zhicheng Wang, Kartik Bhamidipati, Raisa Y. Kiseleva, Carlos H. Villa, Colin Fred Greineder, Scott E. Kasner, Drew Weissman, Michael J. Mitchell, Silvia Muro, Yuri Persidsky, Jacob Samuel Brenner, Vladimir R. Muzykantov, Oscar A. Marcos-Contreras

ACS Nano· Volume 17· Issue 14
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Source abstract

Abstract

Ex vivo -loaded white blood cells (WBC) can transfer cargo to pathological foci in the central nervous system (CNS). Here we tested affinity ligand driven in vivo loading of WBC in order to bypass the need for ex vivo WBC manipulation. We used a mouse model of acute brain inflammation caused by local injection of tumor necrosis factor alpha (TNF-α). We intravenously injected nanoparticles targeted to intercellular adhesion molecule 1 (anti-ICAM/NP). We found that (A) at 2 h, >20% of anti-ICAM/NP were localized to the lungs; (B) of the anti-ICAM/NP in the lungs >90% were associated with leukocytes; (C) at 6 and 22 h, anti-ICAM/NP pulmonary uptake decreased; (D) anti-ICAM/NP uptake in brain increased up to 5-fold in this time interval, concomitantly with migration of WBCs into the injured brain. Intravital microscopy confirmed transport of anti-ICAM/NP beyond the blood–brain barrier and flow cytometry demonstrated complete association of NP with WBC in the brain (98%). Dexamethasone-loaded anti-ICAM/liposomes abrogated brain edema in this model and promoted anti-inflammatory M2 polarization of macrophages in the brain. In vivo targeted loading of WBC in the intravascular pool may provide advantages of coopting WBC predisposed to natural rapid mobilization from the lungs to the brain, connected directly via conduit vessels.
Source: openalex_inverted_index · Quality: baseline

Research context

Nanomaterials

OpenAlex topics: Extracellular vesicles in disease · Neuroinflammation and Neurodegeneration Mechanisms · Barrier Structure and Function Studies

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States

Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, Pennsylvania 19140, United States

Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania 19140, United States

Department of Pathology and Laboratory Medicine, Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States

Center for Cellular Immunotherapies, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States

Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States

Division of Pulmonary Allergy, and Critical Care, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States

School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, Pennsylvania 19104, United States

Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States

Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States

Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States

Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States

Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States

Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States

Institute for Bioengineering of Catalonia (IBEC), Barcelona, 08028, Spain

Institute of Catalonia for Research and Advanced Studies (ICREA), Barcelona, 08010, Spain

Institute for Bioscience and Biotechnology (IBBR), College Park, Maryland 20850, United States

Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania 19140, United States

Funding

National Center for Advancing Translational Sciences · National Cancer Institute · National Institute of Diabetes and Digestive and Kidney Diseases · National Heart, Lung, and Blood Institute · American Heart Association · American Cancer Society · Burroughs Wellcome Fund · Cardiovascular Institute,University of Pennsylvania

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