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Dual-ligand curcin-loaded hybrid solid lipid nanoparticles achieve durable gliosarcoma remission while preserving
Mohamed Sheikh Mohamed1,2, Srivani Veeranarayanan1,3, Yasushi Sakamoto4
1Bio-Nano Electronics Research Centre, Toyo University, 2100 Kujirai, Kawagoe, Saitama, 350-8585, Japan.
Theranostics
|April 17, 2026
Summary
This study developed a novel nanoparticle system for delivering curcin, a potent toxin, to treat aggressive gliosarcoma (GSM). The treatment led to significant tumor regression and extended survival in animal models, offering new hope for this rare brain cancer.
Area of Science:
- Nanomedicine
- Oncology
- Neuroscience
Background:
- Gliosarcoma (GSM) is a rare, aggressive glioblastoma subtype with poor prognosis and limited treatment options.
- Effective drug delivery across the blood-brain barrier (BBB) remains a significant challenge for CNS malignancies.
Purpose of the Study:
- To develop and evaluate a dual-ligand hybrid solid lipid nanoparticle (HSLN) system for targeted delivery of curcin to orthotopic GSM.
- To assess the system's ability to penetrate the BBB, enhance therapeutic efficacy, and preserve neurobehavioral function.
Main Methods:
- Co-functionalization of HSLNs with transferrin and RGD peptides for enhanced BBB penetration and tumor uptake.
- In vivo evaluation of physicochemical properties, cytotoxicity, biodistribution, proteomics, and therapeutic efficacy in orthotopic GSM mouse models.
- Molecular docking studies to investigate curcin's interaction with GSM-associated receptors.
Main Results:
- Dual-ligand HSLNs demonstrated efficient BBB penetration and selective tumor accumulation.
- Curcin-loaded HSLNs achieved complete tumor regression in up to 90% of mice and significantly extended survival.
- Treatment preserved neurobehavioral function and suppressed key tumor-promoting factors like VEGFA/C and MMP-9.
Conclusions:
- Stoichiometry-optimized dual-ligand HSLNs provide a targeted, BBB-penetrant delivery platform for curcin in GSM.
- This approach achieves durable GSM remission with functional preservation, showing promise for CNS malignancies.
- The theranostic-ready platform combines therapeutic potency with tumor specificity for ribosome-inactivating protein delivery.
