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BNC研究助手が参画する共同研究の研究成果が Theranostics誌 に掲載されました
BNC研究助手が参画する共同研究の研究成果が Theranostics誌 に掲載されました
Research results from a collaborative project between Toyo University and Saitama Medical University have been published in the journal Theranostics
English below
主なポイント
• 血液脳関門（BBB）を通過し、グリオサルコーマ腫瘍へ選択的に集積するデュアル標的ハイブリッド固体脂質ナノ粒子（HSLN）を開発しました。
• 本ナノ粒子は、毒性や不安定性のため全身投与が難しい植物由来の抗がんタンパク質クルシンを腫瘍へ送達します。
• 前臨床グリオサルコーマモデルにおいて、最大90％の動物で腫瘍の完全消失が確認され、神経機能および行動機能も維持されました。
• 本研究は、BBBを通過するナノ医薬戦略によって、高い割合のグリオサルコーマ制御を示した初期の報告の一つです。
研究概要
グリオサルコーマは、血液脳関門（BBB）の存在により多くの抗がん剤が脳腫瘍へ到達できないため、治療が極めて困難な悪性脳腫瘍の一つです。本研究では、トランスフェリンおよびRGDリガンドで修飾したデュアル標的ハイブリッド固体脂質ナノ粒子を開発し、BBBを越えて腫瘍へ効率的に到達するナノ医薬プラットフォームを構築しました。
このナノ粒子は、強力な抗腫瘍活性を持つリボソーム不活化タンパク質クルシンを送達します。最適化されたナノ粒子（約150〜200 nm）は腫瘍組織に効率的に集積し、最大48時間腫瘍内に留まることで、持続的な薬剤作用を可能にしました。
その結果、血管新生および腫瘍形成に関連する分子経路が抑制され、顕著な腫瘍退縮が確認されました。特に独立した検証モデルでは、最大90％の動物で腫瘍の完全消失が観察されました。このような高い割合でグリオサルコーマ制御を示した結果は、BBB透過型ナノ医薬による治療戦略として、これまでにほとんど報告例のない重要な成果と考えられます。
さらに、本研究で開発されたナノ粒子プラットフォームはBBBを効率的に通過する特性を有しており、グリオサルコーマ以外の悪性脳腫瘍や中枢神経系疾患への治療応用にも展開可能なナノ医薬基盤技術として期待されます。
本研究は東洋大学と埼玉医科大学の共同研究として実施され、学術誌 Theranostics に掲載されました。
東洋大学バイオ・ナノエレクトロニクス研究センター
Mohamed Sheikh Mohamed
論文情報
Mohamed MS, Veeranarayanan S, Sakamoto Y, Suge R, Hirosawa N, Poulose AC, Mizuki T, Maekawa T. Dual-ligand curcin-loaded hybrid solid lipid nanoparticles achieve durable gliosarcoma remission while preserving neuro-behavioral function. Theranostics 2026; 16(10):5150-5174. doi:10.7150/thno.123534. https://www.thno.org/v16p5150.htm
Key Points
• Researchers developed dual-targeted hybrid solid lipid nanoparticles (HSLNs) capable of crossing the blood–brain barrier and selectively accumulating in gliosarcoma tumors.
• The nanoparticles deliver curcin, a potent plant-derived cytotoxic protein that is otherwise difficult to administer systemically due to toxicity and instability.
• In preclinical gliosarcoma models, the treatment resulted in complete tumor elimination in up to 90% of treated animals, with preservation of neurological and behavioral function.
• The study represents one of the first demonstrations of durable gliosarcoma control at such a high rate using a blood–brain barrier-penetrating nanoparticle strategy.
Background: Challenges in Treating Gliosarcoma
Gliosarcoma (GSM) is a rare and highly aggressive brain tumor with limited treatment options. One of the major barriers to effective therapy is the blood–brain barrier (BBB), which prevents most anticancer drugs from reaching tumors within the brain. In addition, GSM tumors are highly heterogeneous, and current treatment strategies can damage surrounding healthy brain tissue, often leading to severe neurological side effects. These challenges continue to limit the clinical effectiveness of many otherwise promising anticancer agents.
Research Approach: Dual-Targeted Hybrid Solid Lipid Nanoparticles
In this study, researchers developed a dual-targeted hybrid solid lipid nanoparticle platform designed to overcome these barriers. The nanoparticles were functionalized with transferrin and RGD ligands, enabling them to utilize complementary biological pathways to cross the blood–brain barrier and selectively accumulate within tumor tissue.
The nanoparticle system was used to deliver curcin, a plant-derived ribosome-inactivating protein with strong anticancer activity. Although curcin has demonstrated potent therapeutic effects, its clinical application has been limited due to systemic toxicity and poor stability when administered directly. This dual-ligand hybrid lipid nanoparticle design integrates complementary transport and tumor-targeting mechanisms within a single nanocarrier, enabling efficient delivery of therapeutic proteins to brain tumors.
Research Results: Durable Tumor Suppression in Preclinical Models
The optimized nanoparticles (approximately 150–200 nm in diameter) demonstrated efficient tumor targeting in preclinical gliosarcoma models. Imaging and biodistribution studies showed that the nanoparticles accumulated within the tumor and remained localized for up to 48 hours, enabling sustained exposure of tumor cells to the therapeutic agent.
This targeted delivery resulted in suppression of key angiogenesis- and oncogenesis-associated molecular pathways, leading to significant tumor regression. In an independent validation model, complete tumor elimination was observed in up to 90% of treated animals, accompanied by long-term survival benefits.
Importantly, behavioral and neurological assessments confirmed that treated animals retained normal brain function, indicating that the therapy effectively eradicated tumor tissue while preserving healthy neural structures.
Significance and Future Perspectives
These findings demonstrate the potential of dual-targeted hybrid nanoparticle systems for overcoming the blood–brain barrier and enabling effective treatment of aggressive brain tumors. To our knowledge, this work represents one of the first reports demonstrating such a high rate of gliosarcoma elimination using a BBB-penetrating nanomedicine strategy.
The results highlight the promise of such targeted nanomedicine platforms for delivering otherwise inaccessible therapeutic proteins to brain tumors and may contribute to the development of new treatment approaches for difficult-to-treat brain cancers.
Publication
Mohamed MS, Veeranarayanan S, Sakamoto Y, Suge R, Hirosawa N, Poulose AC, Mizuki T, Maekawa T. Dual-ligand curcin-loaded hybrid solid lipid nanoparticles achieve durable gliosarcoma remission while preserving neuro-behavioral function. Theranostics 2026; 16(10):5150-5174. doi:10.7150/thno.123534. https://www.thno.org/v16p5150.htm
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