A self-amplified nanocatalytic system for achieving "1 + 1 + 1 > 3" chemodynamic therapy on triple negative breast cancer.
A self-amplified nanocatalytic system for achieving "1 + 1 + 1 > 3" chemodynamic therapy on triple negative breast cancer.
复制标题
一种自放大纳米催化系统，可实现三阴性乳腺癌的-1-1-1-1-3-3化学动力学治疗
DOI：
10.1186/s12951-021-00998-y
复制
发表时间：
2021-09-04
影响因子：
10.2
通讯作者：
Shi S
中科院分区：
文献类型：
--
作者：
Zhou L;Chen J;Sun Y;Chai K;Zhu Z;Wang C;Chen M;Han W;Hu X;Li R;Yao T;Li H;Dong C;Shi S
化学动力学疗法(CDT)是一种利用Fenton或类Fenton催化剂将过氧化氢(H_2O_2)转化为有毒的羟基自由基(·OH)来杀伤肿瘤细胞的方法，具有很高的选择性，在肿瘤治疗中具有广阔的应用前景。然而，由于肿瘤细胞内过氧化氢水平不足，治疗效果受到明显限制。幸运的是，β-Lapachone(LAPA)在烟酰胺腺嘌呤二核苷酸(磷酸)NAD(P)H：Q氧化还原酶-1(NQO_1)的催化下能够发挥补充H_2O_2的功能，为解决这一问题提供了新的思路。然而，高水平的活性氧引起的广泛DNA损伤可触发聚(ADP-核糖)聚合酶(PARP)的过度激活，导致H_2O_2供应严重中断，进而降低CDT的疗效。在这里，我们报告了一个自我放大的纳米催化系统(ZIF67/OLA/LAPA)，它可以共同传递PARP抑制剂Olararib(Ola)和NQO1生物激活药物LAPA，以实现可持续的过氧化氢生产和增强CDT(“1 + 1 + 1 >； 3”)。OLA对PARP的有效抑制可以协同LAPA通过NQO1氧化还原循环促进H_2O_2的生成。反过来，高水平的H_2O_2进一步与Co2+反应，通过类Fenton反应产生剧毒的·OH，显著提高CDT。体内外研究表明，ZIF67/OLA/LAPA在NQO1过表达的MDA-MB-231肿瘤细胞中具有良好的抗肿瘤活性。重要的是，由于NQO1的低表达，该纳米复合材料在正常组织中的全身毒性最小。这种纳米催化体系的设计为将PARP抑制剂、NQO1可生物激活药物和Fenton试剂相结合以获得肿瘤特异性自扩增CDT持续产生H_2O_2提供了新的范式。网上版载有补充材料，可在10.1186/s12951-021-00998-y查阅。
Chemodynamic therapy (CDT), employing Fenton or Fenton-like catalysts to convert hydrogen peroxide (H2O2) into toxic hydroxyl radicals (·OH) to kill cancer cells, holds great promise in tumor therapy due to its high selectivity. However, the therapeutic effect is significantly limited by insufficient intracellular H2O2 level in tumor cells. Fortunately, β-Lapachone (Lapa) that can exert H2O2-supplementing functionality under the catalysis of nicotinamide adenine dinucleotide (phosphate) NAD(P)H: quinone oxidoreductase-1 (NQO1) enzyme offers a new idea to solve this problem. However, extensive DNA damage caused by high levels of reactive oxygen species can trigger the “hyperactivation” of poly(ADP-ribose) polymerase (PARP), which results in the severe interruption of H2O2 supply and further the reduced efficacy of CDT. Herein, we report a self-amplified nanocatalytic system (ZIF67/Ola/Lapa) to co-deliver the PARP inhibitor Olaparib (Ola) and NQO1-bioactivatable drug Lapa for sustainable H2O2 production and augmented CDT (“1 + 1 + 1 > 3”). The effective inhibition of PARP by Ola can synergize Lapa to enhance H2O2 formation due to the continuous NQO1 redox cycling. In turn, the high levels of H2O2 further react with Co2+ to produce the highly toxic ·OH by Fenton-like reaction, dramatically improving CDT. Both in vitro and in vivo studies demonstrate the excellent antitumor activity of ZIF67/Ola/Lapa in NQO1 overexpressed MDA-MB-231 tumor cells. Importantly, the nanocomposite presents minimal systemic toxicity in normal tissues due to the low NQO1 expression. This design of nanocatalytic system offers a new paradigm for combing PARP inhibitor, NQO1-bioactivatable drug and Fenton-reagents to obtain sustained H2O2 generation for tumor-specific self-amplified CDT. The online version contains supplementary material available at 10.1186/s12951-021-00998-y.
登录
查看更多内容
影响因子：
50.3
作者：
Huang X;Motea EA;Moore ZR;Yao J;Dong Y;Chakrabarti G;Kilgore JA;Silvers MA;Patidar PL;Cholka A;Fattah F;Cha Y;Anderson GG;Kusko R;Peyton M;Yan J;Xie XJ;Sarode V;Williams NS;Minna JD;Beg M;Gerber DE;Bey EA;Boothman DA
通讯作者：
Boothman DA
疏通化学动力学疗法协同离子疗法的障碍，促进肿瘤治疗
影响因子：
15.1
作者：
Liu, Junjie;Jin, Yajie;Shi, Jinjin
通讯作者：
Shi, Jinjin
影响因子：
9.5
作者：
Wu, Fan;Zhang, Qicheng;Li, Ao
通讯作者：
Li, Ao
通过纳米催化剂递送，肿瘤选择性催化纳米医学。
影响因子：
16.6
作者：
Huo M;Wang L;Chen Y;Shi J
通讯作者：
Shi J
影响因子：
17.1
作者：
Li, Wei-Peng;Su, Chia-Hao;Yeh, Chen-Sheng
通讯作者：
Yeh, Chen-Sheng