Nitric Oxide Nanotechnology Normalizes Tumor Vessels and Boosts Cancer Therapy 以奈米一氧化氮技術正常化腫瘤血管

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umors often grow abnormal, leaky blood vessels that actually make treatment less effective by limiting drug delivery and creating a low-oxygen, immune-suppressive environment. We developed a nanoscale nitric oxide delivery system called NanoNO that slowly and precisely releases nitric oxide inside liver tumors. At low doses, NanoNO does not destroy blood vessels—instead, it “normalizes” them, improving blood flow, reducing hypoxia, and allowing chemotherapy drugs and therapeutic proteins to penetrate tumors more effectively. Even more importantly, NanoNO reshapes the tumor microenvironment by reducing immune suppression and increasing cancer-fighting T cell infiltration. In animal models, this strategy significantly enhanced the effects of chemotherapy, protein-based therapies, and cancer vaccines. By using nanotechnology to carefully control nitric oxide release, we turn dysfunctional tumor blood vessels from a barrier into a therapeutic advantage.

腫瘤內的血管往往異常、彎曲又滲漏，導致血流不穩定、缺氧嚴重，使藥物難以深入腫瘤核心，也讓免疫細胞無法有效發揮作用。我們開發了一種名為 NanoNO 的奈米一氧化氮傳遞系統，能穩定且持續地釋放一氧化氮（NO）到腫瘤內。在低劑量下，NanoNO 不會破壞血管，反而能「正常化」腫瘤血管，改善血流、減少缺氧，讓化療藥物與蛋白質藥物更容易進入腫瘤。同時，NanoNO 也能重新調整腫瘤的免疫微環境，增加殺癌 T 細胞的浸潤，提升免疫治療效果。在動物模型中，NanoNO 與化療、標靶蛋白或癌症疫苗合併使用，都展現出更強的抗腫瘤效果。我們的研究證明，透過精準控制一氧化氮的奈米傳遞，可以把原本阻礙治療的腫瘤血管，轉變為幫助治療的關鍵突破點。

Delivery of Nitric Oxide with a Nanocarrier Promotes Tumour Vessel Normalization and Potentiates Anti-Cancer Therapies. Nature Nanotechnology, 14, 1160–1169.