Reprogramming Liver Cancer with Dual-Targeted Immunogene Nanoparticles 具腫瘤特異性的奈米基因載體系統

Cancer can avoid immune attack by expressing molecules like PD-L1 that suppress T cells and by creating a tumor environment that weakens immune responses. To overcome this, we developed a tumor-selective nanoparticle system that delivers two genetic therapies at the same time: siRNA to silence PD-L1 and plasmid DNA to produce the immune-stimulating cytokine IL-2 directly inside liver tumors. This dual-delivery approach both removes the tumor’s “immune brake” and boosts cancer-killing T cells within the tumor. The nanoparticles are engineered to efficiently target cancer cells and release their genetic cargo, and the carrier itself helps activate immune signaling pathways that strengthen anti-tumor immunity. In animal models, this strategy significantly reduced tumor growth and metastasis, especially when combined with a cancer vaccine, highlighting the power of combining nanotechnology with immunotherapy to fight cancer more effectively.

癌細胞常透過表現 PD-L1 等分子來抑制免疫系統攻擊，同時營造出一個免疫抑制的腫瘤微環境，使治療效果大打折扣。為了解決這個問題，我們開發了一種具腫瘤選擇性的奈米載體系統，同時運送兩種基因治療策略：以 siRNA 關閉 PD-L1 的表現，解除腫瘤對免疫細胞的「煞車」，並以質體 DNA 讓腫瘤內部產生免疫活化細胞激素 IL-2，提升殺癌 T 細胞的活性。這種雙重基因傳遞設計，不僅能有效進入肝癌細胞並釋放基因貨物，奈米載體本身還能啟動先天免疫相關訊號路徑，加強整體抗腫瘤反應。在動物模型中，這種策略顯著抑制腫瘤生長與遠端轉移，若再搭配癌症疫苗效果更佳，展現出結合奈米科技與免疫治療的強大潛力。

Highly Efficient and Tumor-Selective Nanoparticles for Dual-Targeted Immunogene Therapy against Cancer. Science Advances, 6(3), eaax5032.