論文 - 詳細
| RRC ID | 87611 |
|---|---|
| 著者 | Mohamed MS, Veeranarayanan S, Sakamoto Y, Suge R, Hirosawa N, Poulose AC, Mizuki T, Maekawa T. |
| タイトル | Dual-ligand curcin-loaded hybrid solid lipid nanoparticles achieve durable gliosarcoma remission while preserving neuro-behavioral function. |
| ジャーナル | Theranostics |
| Abstract |
RATIONALE:Gliosarcoma (GSM) is a rare, highly invasive glioblastoma subtype with limited therapeutic options and a poor prognosis. We report the first dual-ligand hybrid solid lipid nanoparticle (HSLN) system for blood-brain barrier (BBB) penetration and targeted delivery of curcin, a type I ribosome-inactivating protein (RIP), to orthotopic GSM. METHODS:HSLNs (~150-200 nm, polydispersity index (PDI) < 0.3, zeta potential (ζ) ≈ -8 mV) were co-functionalized with transferrin and RGD peptides at optimized 4:6 ratios to enhance BBB transcytosis and tumor uptake. Physicochemical, cytotoxicity, and docking studies assessed curcin stability, bioactivity, and multi-receptor interactions. In vivo biodistribution, proteomics, and therapeutic efficacy were evaluated in BALB/c-nu and ICR-nu orthotopic GSM models, with neurobehavioral assessments for functional preservation. RESULTS:Intravenous curcin-loaded dual-ligand HSLNs achieved complete tumor regression in 60% of BALB/c-nu and 90% of ICR-nu mice, extending median survival from 14 to 38 days in BALB/c-nu mice and resulting in median survival not reached in an independent ICR-nu cohort. Neurobehavioral function was preserved during treatment. Biodistribution and proteomic analyses confirmed efficient BBB penetration, tumor-selective accumulation, and suppression of VEGFA/C, MMP-9, PDGFB, and SERPINE1. Molecular docking revealed strong binding of curcin to GSM-associated receptors (EGFR, EphA2, mGluR6, and IL-13Rα2). CONCLUSIONS:Stoichiometry-optimized dual-ligand HSLNs enable targeted, BBB-penetrant delivery of curcin, achieving durable GSM remission with functional preservation. This theranostic-ready platform combines therapeutic potency with tumor specificity, offering a promising strategy for ribosome-inactivating protein delivery in GSM and other CNS malignancies. |
| 巻・号 | 16(10) |
| ページ | 5150-5174 |
| 公開日 | 2026-1-1 |
| DOI | 10.7150/thno.123534 |
| PII | thnov16p5150 |
| PMID | 41993637 |
| PMC | PMC13080334 |
| MeSH | Animals Blood-Brain Barrier / metabolism Brain Neoplasms* / drug therapy Cell Line, Tumor Female Gliosarcoma* / drug therapy Gliosarcoma* / pathology Humans Ligands Lipids / chemistry Liposomes Mice Mice, Inbred BALB C Mice, Inbred ICR Mice, Nude Nanoparticles* / administration & dosage Nanoparticles* / chemistry Tissue Distribution |
| IF | 8.579 |
| リソース情報 | |
| ヒト・動物細胞 | GI-1(RCB0763) |