ArticleNature nanotechnology2022
Supramolecular arrangement of protein in nanoparticle structures predicts nanoparticle tropism for neutrophils in acute lung inflammation.
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Article in Nature nanotechnology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53citing papers in PubMed
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53 citing papers in PubMed, 112 citations in OpenAlex.
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- Nanoengineered Macrophages for in vivo Three-Dimensional Photoacoustic Imaging and Immunotherapy of Acute Lung Injury.International journal of nanomedicine · 2026Article
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- Harnessing biomaterials for tuning inflammation: A neutrophil-centric perspective.Materials today. Bio · 2025Review
- Designing the Next Generation of Biomaterials through Nanoengineering.Advanced materials (Deerfield Beach, Fla.) · 2025Review
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- Nanoparticle-Based Pulmonary Immune Engineering.Annual review of chemical and biomolecular engineering · 2025Review
- Inhalable nanocatalytic therapeutics for viral pneumonia.Nature materials · 2025Article
- Identification of splenic IRF7 as a nanotherapy target for tele-conditioning myocardial reperfusion injury.Nature communications · 2025Article
- Conjugation Chemistry Markedly Impacts Toxicity and Biodistribution of Targeted Nanoparticles, Mediated by Complement Activation.Advanced materials (Deerfield Beach, Fla.) · 2025Article
- Neutrophil-avid nanocarrier uptake by STAT3 dominant-negative hyper-IgE syndrome patient neutrophils.Life science alliance · 2024Article
- Cell-mediated nanoparticle delivery systems: towards precision nanomedicine.Drug delivery and translational research · 2024Review
- Protein isoform-centric therapeutics: expanding targets and increasing specificity.Nature reviews. Drug discovery · 2024Review
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Authors and funding
29 authors at 4 institutions in 1 country.
Jacob W Myerson *Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Priyal N Patel *Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Kathryn M Rubey *Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-2359-5628
Marco E ZamoraDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-7858-307X
Michael H ZaleskiDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-8419-1718
Nahal HabibiBiointerfaces Institute and Department of Chemical Engineering, University of Michigan at Ann Arbor, Ann Arbor, MI, USA.
Landis R WalshDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Yi-Wei LeeDepartment of Chemistry, University of Massachusetts at Amherst, Amherst, MA, USA.
David C LutherDepartment of Chemistry, University of Massachusetts at Amherst, Amherst, MA, USA.
Laura T FergusonDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Oscar A Marcos-ContrerasDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Patrick M GlassmanDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-3786-0437
Liudmila L MazaleuskayaDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-7955-0379
Ian JohnstonDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Elizabeth D HoodDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Tea ShuvaevaDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-5156-6088
Jichuan WuDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Hong-Ying ZhangDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jason V GregoryBiointerfaces Institute and Department of Chemical Engineering, University of Michigan at Ann Arbor, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-7964-2027
Raisa Y KiselevaDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jia NongDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Tilo GrosserDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Colin F GreinederDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Samir MitragotriJohn A Paulson School of Engineering & Applied Sciences and Wyss Institute, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-2459-8305
George S WorthenDepartment of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Vincent M RotelloDepartment of Chemistry, University of Massachusetts at Amherst, Amherst, MA, USA.ORCID http://orcid.org/0000-0002-5184-5439
Joerg LahannBiointerfaces Institute and Department of Chemical Engineering, University of Michigan at Ann Arbor, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-3334-2053
Vladimir R MuzykantovDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jacob S BrennerDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. jacob.brenner@pennmedicine.upenn.edu.ORCID http://orcid.org/0000-0001-8437-0161
Translational Therapeutics (United States) · USUniversity of Michigan · USUniversity of Pennsylvania · USHarvard University · US
Funding
Phenotypic Diversity in COVID-19UL1TR001878 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2016 to 2025
$102.4MTraining in Molecular Therapeutics for Pediatric CardiologyT32HL007915 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI Robert J Levy, JOSEPH W ROSSANO · 1999 to 2026
$13.4MVascular Targeting of Nanocarriers for RNAR01HL155106 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R, WEISSMAN, DREW · 2021 to 2024
$3.1MTargeting of Bio-orthogonal Chemotherapeutic Nanozymes to Tumor-Associated MacrophagesR01EB022641 · NIBIB · UNIVERSITY OF MASSACHUSETTS AMHERST · PI ROTELLO, VINCENT M. · 2017 to 2024
$3.0MDual drug delivery to lung/blood interface in respiratory infections.R01HL157189 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2021 to 2024
$2.9MControlling complement to unleash nanomedicine for acute critical illnessesR01HL160694 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI BRENNER, JACOB, MUZYKANTOV, VLADIMIR R · 2022 to 2025
$2.7MTargeted nanomedicine for ALI and I/RR01HL125462 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2015 to 2018
$2.3MNanomedicine for ARDS: A new paradigm to target drugs to multiple cell types within alveolar capillariesR01HL153510 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI BRENNER, JACOB · 2020 to 2024
$2.0MNanonscale drug carriers for the treatment of acute respiratory distress syndromeK08HL138269 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI BRENNER, JACOB · 2017 to 2021
$746kICAM-1 targeted thrombomodulin: an experimental therapeutic for the Acute Respiratory Distress SyndromeK08HL130430 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI GREINEDER, COLIN FRED · 2016 to 2020
$665kDevelopment of Neutrophil-Avid Nanocarriers as an Antibiotic Delivery SystemF32HL151026 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI RUBEY, KATHRYN · 2020 to 2022
$238kNanoscale drug carriers for the treatment of Acute Respiratory Distress Syndrome (ARDS).F31HL154662 · NHLBI · DREXEL UNIVERSITY · PI ZAMORA, MARCO E · 2020 to 2023
$186kNCATS NIH HHS UL1 TR001878NHLBI NIH HHS F31 HL154662NHLBI NIH HHS F32 HL151026NHLBI NIH HHS K08 HL130430NHLBI NIH HHS K08 HL138269NHLBI NIH HHS R01 HL125462NHLBI NIH HHS R01 HL153510NHLBI NIH HHS R01 HL155106NHLBI NIH HHS R01 HL157189NHLBI NIH HHS R01 HL160694NHLBI NIH HHS T32 HL007915NIBIB NIH HHS R01 EB022641
Abstract
This study shows that the supramolecular arrangement of proteins in nanoparticle structures predicts nanoparticle accumulation in neutrophils in acute lung inflammation (ALI). We observed homing to inflamed lungs for a variety of nanoparticles with agglutinated protein (NAPs), defined by arrangement of protein in or on the nanoparticles via hydrophobic interactions, crosslinking and electrostatic interactions. Nanoparticles with symmetric protein arrangement (for example, viral capsids) had no selectivity for inflamed lungs. Flow cytometry and immunohistochemistry showed NAPs have tropism for pulmonary neutrophils. Protein-conjugated liposomes were engineered to recapitulate NAP tropism for pulmonary neutrophils. NAP uptake in neutrophils was shown to depend on complement opsonization. We demonstrate diagnostic imaging of ALI with NAPs; show NAP tropism for inflamed human donor lungs; and show that NAPs can remediate pulmonary oedema in ALI. This work demonstrates that structure-dependent tropism for neutrophils drives NAPs to inflamed lungs and shows NAPs can detect and treat ALI.
Indexed as
Acute DiseaseAgglutinationAnimalsAntibodiesCross-Linking ReagentsDextransHumansInflammationLipopolysaccharidesLiposomesLungMaleMiceMice, Inbred C57BLMuramidaseNanoparticlesAntibodiesCross-Linking ReagentsDextransLipopolysaccharidesLiposomesMuramidaseOpsonin ProteinsProteins
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