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Peer-reviewedCC BY-NC-NDBioactive materials

Inhaled nanogels ameliorate vascular remodeling in pulmonary arterial hypertension via normalization of endothelia-smooth muscle cell crosstalk

  • Yuanping Shi1
  • Jing Wu1
  • Ce Chao2
  • Yuheng Lei3
  • Huilin Tang4
  • Yang Zhou3
  • Bin Wang2
  • Yuansong Wei3
  • Lichen Yin2
4 affiliations
  1. 1Basic Medical Research Center, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China
  2. 2Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China
  3. 3Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory of Advanced Healthcare Materials & Devices, Soochow University, Suzhou, 215123, China
  4. 4Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China
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Abstract

Maintaining appropriate vascular nitric oxide (NO) levels in pulmonary arteries is crucial for the alleviation of pulmonary arterial hypertension (PAH). However, in the injured vascular microenvironment, excessive reactive oxygen species (ROS) deplete NO to generate peroxynitrite, which aggravates the oxidative stress and endothelial dysfunction. Herein, ROS-responsive, zwitterionic nanogels (NGs), containing arginine pendants as NO precursors and encapsulating resveratrol (RSV) as an anti-oxidant, were developed for PAH management via inhalation. Benefiting from their zwitterionic surface that repels mucin adsorption, the inhaled NGs exhibit effective pulmonary mucus penetration and mucosal absorption, enabling robust diffusion to the injured pulmonary arteries. In the oxidative vascular microenvironment, the diselenide crosslinkers within the NGs are cleaved, promoting NGs dissociation and on-demand RSV release. The released RSV scavenges ROS and the arginine pendants are oxidized to generate NO, which cooperate to interrupt the ROS/NO disequilibrium. In a hypoxia/SU5416-induced PAH mouse model, inhaled NGs efficiently alleviate vascular remodeling and reduce pulmonary arterial pressure. This study offers an effective strategy for pulmonary drug delivery, and holds promising potentials for the management of PAH.

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Cite

BibTeXRIS
BibTeX
@article{shi2026inhaled,
  title = {{Inhaled nanogels ameliorate vascular remodeling in pulmonary arterial hypertension via normalization of endothelia-smooth muscle cell crosstalk}},
  author = {Yuanping Shi and Jing Wu and Ce Chao and Yuheng Lei and Huilin Tang and Yang Zhou and Bin Wang and Yuansong Wei and Lichen Yin},
  journal = {Bioactive materials},
  year = {2026},
  month = oct,
  doi = {10.1016/j.bioactmat.2026.09.045},
  url = {https://europepmc.org/article/PMC/PMC13717037},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Inhaled nanogels ameliorate vascular remodeling in pulmonary arterial hypertension via normalization of endothelia-smooth muscle cell crosstalk
AU  - Yuanping Shi
AU  - Jing Wu
AU  - Ce Chao
AU  - Yuheng Lei
AU  - Huilin Tang
AU  - Yang Zhou
AU  - Bin Wang
AU  - Yuansong Wei
AU  - Lichen Yin
PY  - 2026
DA  - 2026/10/22
JO  - Bioactive materials
DO  - 10.1016/j.bioactmat.2026.09.045
UR  - https://europepmc.org/article/PMC/PMC13717037
AB  - Maintaining appropriate vascular nitric oxide (NO) levels in pulmonary arteries is crucial for the alleviation of pulmonary arterial hypertension (PAH). However, in the injured vascular microenvironment, excessive reactive oxygen species (ROS) deplete NO to generate peroxynitrite, which aggravates the oxidative stress and endothelial dysfunction. Herein, ROS-responsive, zwitterionic nanogels (NGs), containing arginine pendants as NO precursors and encapsulating resveratrol (RSV) as an anti-oxidant, were developed for PAH management via inhalation. Benefiting from their zwitterionic surface that repels mucin adsorption, the inhaled NGs exhibit effective pulmonary mucus penetration and mucosal absorption, enabling robust diffusion to the injured pulmonary arteries. In the oxidative vascular microenvironment, the diselenide crosslinkers within the NGs are cleaved, promoting NGs dissociation and on-demand RSV release. The released RSV scavenges ROS and the arginine pendants are oxidized to generate NO, which cooperate to interrupt the ROS/NO disequilibrium. In a hypoxia/SU5416-induced PAH mouse model, inhaled NGs efficiently alleviate vascular remodeling and reduce pulmonary arterial pressure. This study offers an effective strategy for pulmonary drug delivery, and holds promising potentials for the management of PAH.
SN  - 2452-199X
ER  -