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paper, - Coggle Diagram

- - - - SU20%H
        
        有最佳的基因轉染潛力
        
        molar ratio of UFA, histamine, and ROS-responsive thioketal linker (Compound 4) = 0.2:0.8:1.2
        
        TPP- terminated SUH molecules =TPP-SUH Ide- terminated SUH molecules =Ide-SUH
        
        用1H NMR 確認結構
        
        用 GPC (凝膠滲透色譜)、1H NMR 確認TPP-SUH/Ide-SUH 的接枝率
  - - - the optimal concentration
        of Ide in Ide-SUH was 2 × 10−6 m.
      - Ide-SUH had the ability to clear ROS (H2O2) and to protect cells from ROS damage
    - - weight ratio of TPP-SUH/DNA 在 40:1 下有最佳轉染效率
      - 與 DNA 的縮合能力有關
  - - - SUH/DNA=118.7 ± 2.3 nm TPP-SUH/DNA=122.9 ± 0.6nm TISUH/DNA= 252.5 ± 2.7 nm nanoparticles
        
        皆為均質球體
        
        TISUH/DNA 的粒徑⽐ TPP-SUH/DNA ⾼ 2 倍的原因
        
        納⽶粒⼦表⾯電荷的變化。引⼊ Ide-SUH 後，TISUH/DNA 複合物的 zeta 電位降低，TISUH 的 DNA 凝聚能力也可能降低，從⽽導致粒徑的增加
        
        Ide 的強疏⽔性，打破了親⽔-疏⽔平衡，顆粒更趨於聚集
  - - - (TISUH/DNA 複合物在眼球和溶酶體微環境中是穩定的，表明 TISUH 具有保護基因免受眼球和溶酶體降解的潛力)
  - - - monitored the amount of DNA released from SUH/DNA complexes following the degradation of SUH via the ethidium bromide (EtBr) exclusion assay (Figure 2C).利用EtBr 觀察SUH 釋放 DNA 的量
      - 利用電泳分析結果與EtBr 相同DNA從 SUH 降解 DNA dissociated from SUH/DNA but not non-UH/DNA when the complexes were exposed to 50 × 10−3 m KO2.(Figure 2D)
    - - 用 FRET 驗證 : (Figure 2F)
        經過 3hr merged 的顏色為黃色(綠+紅) 代表 DNA 未被 release 經過 8hr TPP-SUH/DNA 和 TISUH/DNA 組merged 的顏色只剩綠色代表 DNA 被 release
        
        結論
        
        DNA was released from TISUH/DNA complexes by the disintegration of the backbone component SUH in a ROS-dependent manner
  - - - TISUH have a good safety
  - - - colocalization correlation (Pearson’s correlation, R)
        
        lysosome/DNA 隨著時間R下降 Mitochondrial/DNA 隨著時間R上升(Figure 3A).
        
        internalized TISUH/DNA complexes escaped from lysosomes so that the loaded DNA could be transferred into the mitochondria.
    - - SUH showed more efficient mitochondrial gene delivery than fluorinationfree SU0%H (Figure 3C)支持此結論.
        
        原因
        
        fluorination enhanced the transmembrane ability of the material.
        
        結論
        
        TISUH possessed the capacity to deliver the loaded DNA into the mitochondrial matrix owing to TPP and fluorination.
        
        TPP played a major role in mitochondrial targeting
        in normal HeLa cells
    - - GFP、PEI 25K、TPP-non-UH
      - 發現
        
        TISUH/mtGFP and TPP-SUH/mtGFP displayed better
        mitochondrial transfection efficacies than the other treatments.
        
        Ide-SUH 不會影響 gene 的表現
        
        TPP-non-SUH showed poor mitochondrial
        transfection efficacy.(Figure 3D–F).
    - - due to
        
        the low mitochondrial uptake rate in the PEI 25K group (Figure 3B,C)
  - - - rotenone (Rot)-induced HeLa cells 模擬 LHON
    - - Figure 4D, 用 FRET 檢驗 was still observed in 5 h
        
        the TISUH/DNA complexes
        were not disassembled when they were in cytoplasm
- - - - 現存只能緩解無法根治
- - - - 提高 gene transfection 效率
      - 從根本上糾正 gene 異常的問題
- - - - 與 mitochondrial complex I 的 ND4 中 histidine 被 arginine 置換有關
      - mt DNA異常會導致
        
        粒線體呼吸鏈功能障礙
        
        ATP合成不足
        
        MMP 下降
        
        能量生產的副產物 ROS 無法被清除
        
        過高 ROS 會導致
        
        破壞 mt DNA、蛋白質、整個粒線體
    - - 現存治療方法
        
        Idebenone (Ide)
        
        緩解 ROS 所造成的傷害
        
        無法修復受損的 gene
        
        停用後仍會復發
        
        暫時性的治療
      - 基因療法
        
        將功能基因引⼊個體體內以糾正突變基因
        
        allotopic expression (異位表達)
        
        將 DNA 導入細胞核
        
        translated mRNA/proteins
        into mitochondria
        
        recover protein function
        
        use viral vector (病毒載體)
        
        風險
        
        high cost
        
        carcinogenesis (致癌作用)
        
        immunogenicity (免疫原性)
        
        兩次的 transmissions 傳遞遭限制
        
        situ mitochondrial gene therapy
        (原位粒線體基因治療法)
        
        use nonviral vector (非病毒載體)
        
        simplify delivery procedure and deliver directly exogenous genes into mitochondria.
        
        困難
        
        double membrane structure of mitochondria 增加 gene 傳遞困難
        
        受損的mitochondria MMP 下降
        
        restrict electrostatic interaction-mediated
        mitochondrial uptake
        
        降低治療療效
  - - - released ND4 gene
        and Ide improved the mitochondrial function by repairing complex I and facilitating electron transfer