ID #1088 Nanoparticles with iRGD-DSPE-PEG for CNS drug delivery and anti-glioma therapy

作者：Qiang Fu, Jiatong Dai, J C Chen, Jianan Li, J Huang, Xia Li, Shiyao Song, Hao Xiong, Yanlai Tang · 发表于：Neuro-Oncology Pediatrics · 年份：2026 · DOI：10.1093/neuped/wuag026.488 · 研究领域：Nanoparticle-Based Drug Delivery、Retinoids in leukemia and cellular processes、Barrier Structure and Function Studies

Abstract Objective This study aimed to construct an arsenic trioxide (ATO)-loaded nanodrug delivery system, termed iRGD-PEG-ATO, using DSPE as the carrier modified with polyethylene glycol (PEG) and conjugated with the tumor-targeting peptide iRGD. The system was designed to overcome the limitations of free ATO, including poor blood-brain barrier (BBB) penetration, rapid systemic clearance, narrow therapeutic window, and lack of tumor-specific distribution, thereby providing a novel strategy for glioma therapy. Methods The targeted nanocarrier iRGD-PEG-ATO was synthesized based on iRGD-DSPE-PEG and the αvβ3 integrin-targeting ligand. The nanoparticles were characterized using XPS, TEM,FTIR. In vitro drug release was evaluated via the dialysis bag method. Cytotoxicity and antitumor efficacy were assessed using MTT and live/dead assays. Flow cytometry was employed to analyze effects on cell apoptosis and cell cycle. An in vitro BBB model co-cultured with U87 glioma cells was established to study the tumor-suppressive effects of different ATO formulations after crossing the BBB. An orthotopic U87-LUC glioma model in nude mice was constructed to evaluate the tumor inhibition and survival benefits of iRGD-PEG-ATO. Ki67 and TUNEL immunohistochemistry were performed to assess its effects on tumor cell proliferation and apoptosis in vivo. Transcriptome sequencing was conducted on cells treated with the nanomaterial. Western blot and IHC were used to examine TGFBR2 protein expression ...