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Peer-reviewedCC BY 4.0Advanced Science

Intranasal Delivery of Gallium–Quercetin Nanoparticles for Multi‐Target Ferroptosis Inhibition in Parkinson's Disease

  • Keyang Xu1
  • Dandan Kou1
  • Xiao Xiao1
  • Bingbing Bai2,3
  • Caide Liu4
  • Mengyao Wu1
  • Yadan Shi1
  • Mengdan Xu1
  • Xiaoyi Cao1
  • Haodi Qi1
  • Shuhua Wu4
  • Jianfeng Zeng1,5
1 more authors
  • Mingyuan Gao1,5,6
6 affiliations
  1. 1Department of Radiology The First Affiliated Hospital of Soochow University School of Radiation Medicine and Protection Soochow University Suzhou China
  2. 2General Dentistry Department The Stomatology Hospital Affiliated of Suzhou Vocational Health College Suzhou China
  3. 3Medical School of Nanjing University Nanjing China
  4. 4The Second Affiliated Hospital of Soochow University Suzhou China
  5. 5Biomedical Basic Research Center (BBRC) of Jiangsu Province Suzhou China
  6. 6School of Life Sciences Soochow University Suzhou China
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Abstract

Ferroptosis contributes to Parkinson's disease (PD) through interconnected processes including iron dysregulation, oxidative stress, and mitochondrial dysfunction, yet current therapies targeting single pathways remain insufficient. Herein, we developed gallium–quercetin nanoparticles (GQNPs) as an intranasally deliverable nanoplatform for multi‐target ferroptosis inhibition. In vitro, GQNPs suppressed ferroptosis by coordinating iron regulation and antioxidation. Ga3 + interfered with transferrin‐mediated iron uptake to restrict iron influx, while quercetin reduced oxidative stress and supported iron homeostasis, thereby decreasing ROS accumulation and improving mitochondrial function. In vivo, intranasal delivery of GQNPs effectively bypassed the blood‐brain barrier to recover motor coordination and cognitive function in PD mice. By integrating iron regulation, antioxidant activity, and mitochondrial protection within a single nanoplatform, this work highlights gallium‐based coordination nanoparticles as a promising therapeutic strategy for ferroptosis‐associated neurodegenerative diseases.

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Cite

BibTeXRIS
BibTeX
@article{xu2026intranasal,
  title = {{Intranasal Delivery of Gallium–Quercetin Nanoparticles for Multi‐Target Ferroptosis Inhibition in Parkinson's Disease}},
  author = {Keyang Xu and Dandan Kou and Xiao Xiao and Bingbing Bai and Caide Liu and Mengyao Wu and Yadan Shi and Mengdan Xu and Xiaoyi Cao and Haodi Qi and Shuhua Wu and Jianfeng Zeng and Mingyuan Gao},
  journal = {Advanced Science},
  year = {2026},
  month = aug,
  doi = {10.1002/advs.77025},
  url = {https://doi.org/10.1002/advs.77025},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Intranasal Delivery of Gallium–Quercetin Nanoparticles for Multi‐Target Ferroptosis Inhibition in Parkinson's Disease
AU  - Keyang Xu
AU  - Dandan Kou
AU  - Xiao Xiao
AU  - Bingbing Bai
AU  - Caide Liu
AU  - Mengyao Wu
AU  - Yadan Shi
AU  - Mengdan Xu
AU  - Xiaoyi Cao
AU  - Haodi Qi
AU  - Shuhua Wu
AU  - Jianfeng Zeng
AU  - Mingyuan Gao
PY  - 2026
DA  - 2026/08/07
JO  - Advanced Science
DO  - 10.1002/advs.77025
UR  - https://doi.org/10.1002/advs.77025
AB  - Ferroptosis contributes to Parkinson's disease (PD) through interconnected processes including iron dysregulation, oxidative stress, and mitochondrial dysfunction, yet current therapies targeting single pathways remain insufficient. Herein, we developed gallium–quercetin nanoparticles (GQNPs) as an intranasally deliverable nanoplatform for multi‐target ferroptosis inhibition. In vitro, GQNPs suppressed ferroptosis by coordinating iron regulation and antioxidation. Ga3 + interfered with transferrin‐mediated iron uptake to restrict iron influx, while quercetin reduced oxidative stress and supported iron homeostasis, thereby decreasing ROS accumulation and improving mitochondrial function. In vivo, intranasal delivery of GQNPs effectively bypassed the blood‐brain barrier to recover motor coordination and cognitive function in PD mice. By integrating iron regulation, antioxidant activity, and mitochondrial protection within a single nanoplatform, this work highlights gallium‐based coordination nanoparticles as a promising therapeutic strategy for ferroptosis‐associated neurodegenerative diseases.
SN  - 2198-3844
ER  -