Development of Versatile Nanoparticle System for Efficient Drug Delivery into Pulmonary Endothelium.
- 1Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, USA.
- 2Division of Neonatology, Phoenix Children's Hospital, Phoenix, USA.
- 3Center for Cancer and Blood Diseases, Phoenix Children's Hospital, Phoenix, USA.
Abstract
Drug delivery precisely to the pulmonary vasculature represents a formidable challenge. Pediatric Acute Respiratory Distress Syndrome (PARDS) is an urgent public health concern accounting for high mortality and long-term morbidity due to severe damage to lung endothelial cells (ECs). Advanced target-specific therapeutic interventions to protect lung vasculature in PARDS are in dire need. FOXF1 protein is a critical mediator of lung angiogenesis and vascular repair after injury. However, whether FOXF1 is a useful pharmacological target for PARDS is unknown. Herein, we developed a universal nanoparticle-based Lung Endothelial Drug Delivery (LEDD) system to deliver hydrophobic small-molecule compounds specifically to lung ECs but not to other cells or organs. Based on single-cell RNA sequencing, FOXF1 expression was decreased in lung ECs in the mouse PARDS model. We used LEDD nanoparticles to restore FOXF1 by delivering a novel FOXF1-activating compound, TanFe[F], which prevents FOXF1 protein degradation. LEDD-TanFe[F] treatment increased FOXF1 protein and its activity in lung ECs in vitro and in vivo. LEDD-TanFe[F] treatment was non-toxic, well-tolerated, and improved mice survival in the PARDS model. LEDD-TanFe[F] reduced endothelial permeability, improved vascular repair, and alveolarization in injured neonatal lungs. LEDD-supported drug delivery precisely to lung ECs is a promising therapeutic approach in PARDS.
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BibTeX
@article{mohammed2026development,
title = {{Development of Versatile Nanoparticle System for Efficient Drug Delivery into Pulmonary Endothelium.}},
author = {Afzaal N Mohammed and Zicheng Deng and Arnab Misra and Marcus Orzabal and Ananya Kondapally and Enhong Li and Jonathan Do and Ying-Wei Lan and Fatemeh Kohram and Hunter Blackburn and Andreas Damianos and Tanya V Kalin and Vladimir V Kalinichenko},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = oct,
doi = {10.1002/advs.78292},
url = {https://europepmc.org/article/MED/42875859},
note = {CC BY},
}
RIS
TY - JOUR
TI - Development of Versatile Nanoparticle System for Efficient Drug Delivery into Pulmonary Endothelium.
AU - Afzaal N Mohammed
AU - Zicheng Deng
AU - Arnab Misra
AU - Marcus Orzabal
AU - Ananya Kondapally
AU - Enhong Li
AU - Jonathan Do
AU - Ying-Wei Lan
AU - Fatemeh Kohram
AU - Hunter Blackburn
AU - Andreas Damianos
AU - Tanya V Kalin
AU - Vladimir V Kalinichenko
PY - 2026
DA - 2026/10/14
JO - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
DO - 10.1002/advs.78292
UR - https://europepmc.org/article/MED/42875859
AB - Drug delivery precisely to the pulmonary vasculature represents a formidable challenge. Pediatric Acute Respiratory Distress Syndrome (PARDS) is an urgent public health concern accounting for high mortality and long-term morbidity due to severe damage to lung endothelial cells (ECs). Advanced target-specific therapeutic interventions to protect lung vasculature in PARDS are in dire need. FOXF1 protein is a critical mediator of lung angiogenesis and vascular repair after injury. However, whether FOXF1 is a useful pharmacological target for PARDS is unknown. Herein, we developed a universal nanoparticle-based Lung Endothelial Drug Delivery (LEDD) system to deliver hydrophobic small-molecule compounds specifically to lung ECs but not to other cells or organs. Based on single-cell RNA sequencing, FOXF1 expression was decreased in lung ECs in the mouse PARDS model. We used LEDD nanoparticles to restore FOXF1 by delivering a novel FOXF1-activating compound, TanFe[F], which prevents FOXF1 protein degradation. LEDD-TanFe[F] treatment increased FOXF1 protein and its activity in lung ECs in vitro and in vivo. LEDD-TanFe[F] treatment was non-toxic, well-tolerated, and improved mice survival in the PARDS model. LEDD-TanFe[F] reduced endothelial permeability, improved vascular repair, and alveolarization in injured neonatal lungs. LEDD-supported drug delivery precisely to lung ECs is a promising therapeutic approach in PARDS.
SN - 2198-3844
ER -