癌症治療是全球關注的重要研究領域，隨著奈米醫學的發展，奈米材料廣泛應用於腫瘤治療。然而，化學動力、光動力、聲動力和光熱治療等方法可能存在一些限制與風險。因此，本研究提出了創新的方案，無需額外使用雷射、超聲波或是添加藥物等方式，利用電活性的脂質膜(Membrane-integrated liposomes, MILs)包覆金奈米粒子(Gold nanoparticles, Au NPs)形成Au@MIL NPs做為電子接收器，誘導癌細胞電子轉移至Au NPs，透過破壞癌細胞內氧化還原平衡的方式達到腫瘤治療效果。
Au NPs因高生物相容性以及獨特的物理化學特性而備受矚目。在本研究中，Au NPs作為電子接受器發揮了關鍵作用。此外，我們利用脂質體融合細菌外膜誘導膜交換(Liposome fusion-induced membrane exchange, LIME)技術取得希瓦氏菌(Shewanella oneidensis MR-1)的脂質膜，其富含豐富的c型細胞色素(c-type cytochromes)，形成電子傳遞鏈。因此 Au@MIL NPs保留MILs的電子轉移特性，進一步結合Au NPs的優勢。具有MILs的Au@MIL NPs通過誘導癌細胞電子流失，進而改變粒線體與內質網的膜電位，造成細胞膜的氧化壓力上升，引發癌細胞凋亡。透過表面電漿共振(Surface plasmon resonance, SPR)和X光吸收近邊緣結構(X-ray absorption near edge structure, XANES)證實電子從癌細胞轉移至Au@MIL NPs。體外實驗中，觀察到癌細胞膜的脂質過氧化現象，且發現較大的奈米粒子具有更佳的治療效果，展現尺寸效應，也成功證實Au@MIL NPs對肝癌和乳癌細胞均有毒殺作用，且對正常細胞無害。最後，在體內抗腫瘤實驗中，使用原位肝腫瘤小鼠模型，在100 nm Au@MIL NPs (1 mL, 300 ppm)治療下顯著抑制腫瘤生長，證明此創新療法在體內外均具優異的療效。

In current cancer treatments, various limitations and risks persist. To enhance therapeutic efficacy and develop innovative strategies, we designed Au@MIL nanoparticles, composed of gold nanoparticles and membrane-integrated liposomes (MILs) derived from Shewanella oneidensis MR-1. These nanoparticles induce autonomous electron transfer in cancer cells, disrupting their redox balance. MILs were obtained via the liposome fusion-induced membrane exchange (LIME) process, and protein electrophoresis confirmed their enrichment in c-type cytochromes, which facilitate electron transfer. Our results show that Au@MIL NPs selectively kill 11 types of cancer cells without harming normal cells and exhibit a size-dependent effect, with 100 nm particles showing superior efficacy. Mitochondrial analysis revealed apoptosis induction via mitochondrial dysfunction and lipid peroxidation in both mitochondria and the endoplasmic reticulum, establishing a non-ROSdependent mechanism. Surface plasmon resonance (SPR) and X-ray absorption near-edge structure (XANES) confirmed electron transfer into Au@MIL NPs. In an orthotopic HCC mouse model, 100 nm Au@MIL NPs (1 mL, 300 ppm) significantly suppressed tumor growth within 14 days, demonstrating strong in vitro and in vivo efficacy. Blood, urine, and organ analyses confirmed excellent biocompatibility and biosafety. This study presents a novel, non-ROS-dependent cancer therapy with promising clinical potential.

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