血液を「隠れ蓑」に使うナノ粒子で、最も治療困難な乳がんに挑む ― 光熱療法・免疫抑制解除・自然免疫活性化の三位一体戦略 ―

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2026-08-21 東北大学

三種陰性乳がん(TNBC)の治療を目的に、東北大学の研究グループが、液体金属ナノ粒子を血液成分で被覆した多機能ナノ粒子「B-LM-DMX-αCD25」を開発した。血液由来の成分を「隠れ蓑」として利用することで免疫細胞による排除を回避し、腫瘍への集積量を約5倍に向上。さらに、制御性T細胞(Treg)を標的とする抗体で腫瘍内の免疫抑制を解除し、近赤外線照射による光熱療法とSTINGアゴニストによる自然免疫活性化を組み合わせた。マウスのTNBCモデルでは原発腫瘍を完全消退させ、肺転移を90%以上抑制し、70日超の長期生存を達成した。光熱効果、免疫抑制解除、自然免疫活性化を一体化した新たな転移がん治療プラットフォームとして期待される。

血液を「隠れ蓑」に使うナノ粒子で、最も治療困難な乳がんに挑む ― 光熱療法・免疫抑制解除・自然免疫活性化の三位一体戦略 ―
図1. 本研究の概念(B-LM-DMX-αCD25の設計と三位一体の治療メカニズム)

<関連情報>

血液細胞に偽装された液体金属ナノ複合体がTreg細胞の枯渇とSTING増幅型光熱免疫を誘導し、転移性トリプルネガティブ乳がんの治療に有効である Blood Cell-Camouflaged Liquid Metal Nanoconjugates Orchestrate Treg Depletion and STING-Amplified Photothermal Immunity for Metastatic Triple-Negative Breast Cancer Therapy

Nina Sang, Eijiro Miyako
Advanced Science  Published:11 August 2026
DOI:https://doi.org/10.1002/advs.77069

ABSTRACT

Triple-negative breast cancer (TNBC) remains highly lethal due to aggressive metastasis and profound immunosuppression by regulatory T cells (Tregs). Here, we present a biomimetic liquid metal (LM)-based photothermal immunotherapeutic nanoplatform exploiting gallium-based LMs to orchestrate cascade amplification of antitumor immunity. The engineered nanoplatform (B–LM–DMX–αCD25) integrates an LM photothermal core with dual immunomodulatory components—anti-CD25 antibody for Treg depletion and stimulator of interferon genes (STING) agonist 5,6-dimethylxanthenone-4-acetic acid (DMX) for innate immune activation—while blood-derived camouflaging enhances immune evasion and tumor accumulation. Quantitative RT-PCR of 13 immune-related genes confirmed STING engagement, robust CD8+ cytotoxic T-cell infiltration, and Treg depletion in treated tumors. This platform operates through three synchronized mechanisms: (1) selective intratumoral Treg depletion dismantling immunosuppression; (2) near-infrared-triggered LM-mediated photothermal therapy (58°C within 5 min) inducing immunogenic cell death and releasing tumor-associated antigens; and (3) STING pathway activation promoting dendritic cell maturation and tumor-specific cytotoxic T-cell responses, collectively transforming immunologically “cold” TNBC into immune-responsive tumors. In orthotopic 4T1 models, the nanoplatform achieves significant tumor regression with enhanced survival, while in metastatic models, it reduces pulmonary metastatic nodules and extends median survival beyond 70 days. This work establishes a paradigm-shifting biomimetic LM-based nanodelivery strategy addressing fundamental immunological barriers in TNBC through coordinated photothermal–immunotherapy, offering a clinically translatable approach for TNBC.

医療・健康
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