3069 - Biomimetic CD47 Red Blood Cell Membrane-Coated Nanoparticles Enhance Spleen Radioprotection in Liver Cancer Radiotherapy

05:00pm - 06:00pm PT

Hall F

Screen: 2

POSTER

Presenter(s)

Shigao Huang, MD, PhD - 323 Hospital of People's Liberation Army, Xian,

S. Huang¹, H. Wang², and L. N. Zhao³; ¹Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaan Xi, China, ²Department of Chemistry, School of Pharmacy, Air Force Medical University,, Xi’an, Shaan Xi, China, ³Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China

Purpose/Objective(s):

Protecting normal tissues and immune organs is essential during tumor radiotherapy to minimize off-target harm. Radiation-induced immune organ damage (RIOD) drives adverse clinical outcomes by amplifying oxidative stress and inflammatory cascades, ultimately undermining therapeutic efficacy. The spleen, as a highly radiosensitive organ, demands targeted protective strategies. Recent advancements leveraging erythrocyte membrane-modified nanocellulators—engineered with CD47 ("don't eat me" signaling) and mannose moieties for spleen-specific targeting—have emerged as a promising platform for precision drug delivery. This study focuses on developing a novel anti-radiation therapeutic drug and investigating its molecular mechanisms to mitigate radiation-induced splenic injury, thereby enhancing radioprotection and treatment outcomes.

Materials/Methods:

Biomimetic CD47 red blood cell membrane-coated nanoparticles (CD47/NPs-TPP-NIT), functionalized with a triphenylphosphine cation and NIT radical, were synthesized. These nanoparticles were evaluated for their radioprotective effects in mice exposed to 6.0 Gy X-ray irradiation. Histopathological analysis of splenic tissues and hematological profiling were performed to assess radiation damage mitigation. Quantitative proteomics identified differentially expressed proteins (DEPs) associated with inflammatory regulation. In vivo experiments further validated the protective efficacy of CD47/NPs-TPP-NIT and its influence on radiotherapy outcomes.

Results:

CD47/NPs-TPP-NIT significantly enhanced antioxidant enzyme activity (superoxide dismutase, catalase, glutathione peroxidase) and reduced malondialdehyde levels and reactive oxygen species (ROS) generation in irradiated spleens. Additionally, it suppressed apoptosis by inhibiting cleaved caspase-3 activation, upregulating anti-apoptotic Bcl-2, and downregulating pro-apoptotic Bax. Mechanistically, CD47/NPs-TPP-NIT blocked radiation-induced IKK/I?B/NF-?B pathway activation, mitigating splenic inflammatory damage. Crucially, in liver tumor-bearing mice, CD47/NPs-TPP-NIT did not protect tumors or interfere with radiotherapy efficacy.

Conclusion:

CD47/NPs-TPP-NIT alleviates radiation-induced splenic injury by inhibiting IKK/I?B/NF-?B signaling, reducing pro-inflammatory cytokine secretion, and promoting anti-inflammatory mediator production. Its selective radioprotection of immune organs, without compromising tumor radiotherapy outcomes, highlights its potential as a promising radioprotective agent to shield immune organs from irradiation-induced damage.