Development of Nanocarrier‐Based Oral Pegfilgrastim Formulations for Mitigating Hematopoietic Acute Radiation Syndrome
The increasing risks of ionizing radiation from deep space travel and nuclear accidents necessitate the development of effective countermeasures. Acute radiation syndrome (ARS), particularly hematopoietic ARS (H-ARS), leads to life-threatening anemia and bone marrow failure, with long-term risks including cancer and cardiovascular disease. This study presents phenylboronic acid-functionalized chitosan-polyethylenimine (CPB) polymers designed for efficient oral delivery of pegfilgrastim (PF), an FDA-approved radioprotective agent. Nanoparticles were prepared through complexation of PF with tannic acid, forming a negatively charged core, followed by encapsulation with a CPB polymer shell. This supramolecular strategy enabled efficient protein condensation into uniform nanoparticles. The nanosystem effectively reduced H-ARS-associated anemia in mice by promoting blood cell reconstitution, supported by <i>in vitro</i> results with human hematopoietic stem/progenitor cells. Additionally, the material reduced toll-like receptor activation in multiple human cell types post-radiation. This system may mitigate radiation injury risks from accidental exposure on Earth and during extended space missions.
Authors
- Guy Garty (ORCID: https://orcid.org/0000-0001-5683-7318)
- Yongqiang Xiao
- Zhehao Zhu (ORCID: https://orcid.org/0000-0001-5655-836X)
- Ilaria Baldassarri (ORCID: https://orcid.org/0000-0002-8515-1080)
- Sally A. Amundson (ORCID: https://orcid.org/0000-0001-9992-8818)
- Brian Ponnaiya
- David J. Brenner (ORCID: https://orcid.org/0000-0002-0926-1210)
- Kam W. Leong (ORCID: https://orcid.org/0000-0002-8133-4955)
- Diogo Teles (ORCID: https://orcid.org/0000-0002-0235-6583)
- Daniel Naveed Tavakol (ORCID: https://orcid.org/0000-0003-0451-0617)
- Naoto Yoshinaga (ORCID: https://orcid.org/0000-0003-4399-0289)
- Xiao Yu Wu (ORCID: https://orcid.org/0000-0002-5333-8115)
- Yuefei Zhu (ORCID: https://orcid.org/0000-0001-7684-2448)
- Gordana Vunjak‐Novakovic (ORCID: https://orcid.org/0000-0002-9382-1574)
- Siyu He (ORCID: https://orcid.org/0009-0007-5788-3595)
- Xuefeng Wu (ORCID: https://orcid.org/0000-0003-0437-2904)
- Derek Ning
- Huaxi Wang
Institutions
- Columbia University (US)
Publication Details
- Journal
- Advanced Functional Materials
- Published
- 2025-02-05
- DOI
- https://doi.org/10.1002/adfm.202421462
- Citations
- 3
- Primary Topic
- Effects of Radiation Exposure
- Type
- article
- Field-Weighted Citation Impact
- 4.08
Funders
- National Science Foundation
- National Aeronautics and Space Administration
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- Irving Medical Center, Columbia University
- National Institute of Allergy and Infectious Diseases