Intracellular Enzyme-Triggered Assembly of Amino Acid-Modified Gold Nanoparticles for Accurate Cancer Therapy with Multimode
Intracellular Enzyme-Triggered Assembly of Amino Acid-Modified Gold Nanoparticles for Accurate Cancer Therapy with Multimode
复制标题
细胞内酶触发的氨基酸修饰金纳米粒子组装，用于多模式精确癌症治疗
DOI：
10.1021/acsami.9b05943
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发表时间：
2019
影响因子：
9.5
通讯作者：
Chen Xin
中科院分区：
文献类型：
--
作者：
Liu Tao;Jin Ronghua;Yuan Pingyun;Bai Yongkang;Cai Bolei;Chen Xin
以亚铁离子（Fe2+）为桥离子，通过配位键制备了具有pH可调的两性离子表面的多氨基酸（谷氨酰胺和赖氨酸）修饰的金纳米粒子a，该纳米粒子能够在肿瘤细胞中自发选择性地组装，用于结合酶触发光热疗法和H2O2依赖的催化药物的精确肿瘤治疗。这些金纳米颗粒在pH 7.4（血液系统）下显示电中性，以防止正常细胞的内吞，而正常细胞在pH 6.8（肿瘤微环境）下可带正电，以促进肿瘤细胞对这些纳米颗粒的内吞，表现出很大的肿瘤选择性。细胞摄取后，肿瘤细胞中的特异性酶（转氨酶）会催化谷氨酰胺和赖氨酸的聚合，导致这些金纳米颗粒在细胞内组装，从而产生优异的光热特性，用于精确的肿瘤治疗。此外，Fe 2+可通过芬顿反应分解肿瘤细胞内过量的过氧化氢（H2O2），产生大量的羟基自由基（·OH）。这些自由基也会导致肿瘤细胞损伤。这种协同治疗与高肿瘤选择性产生了8倍，在体外对肿瘤细胞的细胞毒性与10分钟的近红外照射下孵育48小时的正常细胞相比。此外，荷瘤裸鼠模型的体内数据显示，在催化药物和光热疗法相结合的多模式治疗3周后，肿瘤可以被完全抑制并逐渐消除。该系统利用三种肿瘤微环境条件（低pH、酶和H2O2）来触发治疗作用，这是一个有前途的癌症治疗平台，可在多种模型中实现延长血液系统循环时间、选择性细胞摄取和准确的肿瘤治疗。
Multiple amino acid (glutamine and lysine)-modified gold nanoparticles a with pH-switchable zwitterionic surface were fabricated through coordination bonds using ferrous iron (Fe2+) as bridge ions, which are able to spontaneously and selectively assemble in tumor cells for accurate tumor therapy combining enzyme-triggered photothermal therapy and H2O2-dependent catalytic medicine. These gold nanoparticles showed electric neutrality at pH 7.4 (hematological system) to prevent endocytosis of normal cells, which could be positively charged at pH 6.8 (tumor microenvironment) to promote the endocytosis of tumor cells to these nanoparticles, performing great tumor selectivity. After cell uptake, the specific enzyme (transglutaminase) in tumor cells would catalyze the polymerization of glutamine and lysine to cause the intracellular assembly of these gold nanoparticles, resulting in an excellent photothermal property for accurate tumor therapy. Moreover, the Fe2+ion could decompose excess hydrogen peroxide (H2O2) in tumor cells via the Fenton reaction, resulting in a large amount of hydroxyl radicals (·OH). These radicals would also cause tumor cell damage. This synergetic therapy associating with high tumor selectivity generated an 8-fold in vitro cytotoxicity against tumor cells compared with normal cells under 48 h incubation with 10 min NIR irradiation. Moreover, in vivo data from tumor-bearing nude mice models showed that tumors can be completely inhibited and gradually eliminated after multimode treatment combining catalytic medicine and photothermal therapy for 3 weeks. This system takes advantage of three tumor microenvironment conditions (low pH, enzyme, and H2O2) to trigger the therapeutic actions, which is a promising platform for cancer therapy that achieved prolonged circulation time in the blood system, selective cellular uptake, and accurate tumor therapy in multiple models.