A smart copper-phthalocyanine framework nanoparticle for enhancing photodynamic therapy in hypoxic conditions by weakening cells through ATP depletion
A smart copper-phthalocyanine framework nanoparticle for enhancing photodynamic therapy in hypoxic conditions by weakening cells through ATP depletion
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一种智能铜酞菁框架纳米颗粒，通过 ATP 耗竭来削弱细胞，从而增强缺氧条件下的光动力治疗
DOI：
10.1039/c8tb00334c
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发表时间：
2018-04-14
影响因子：
7
通讯作者：
Wei, Shaohua
中科院分区：
文献类型：
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作者：
Gui, Li;Zhou, Jiahong;Wei, Shaohua
实体肿瘤中的缺氧会阻碍光动力疗法（PDT）的疗效。在缺氧肿瘤细胞中生成三磷酸腺苷（ATP）的途径包括无效的糖酵解过程，但ATP对快速和不受控制的生长和分裂至关重要。ATP耗竭会抑制DNA复制和谷胱甘肽（GSH）的合成，从而抑制细胞增殖，使其对PDT敏感。在此背景下，设计并制备了由Cu 2+和羧基修饰的酞菁锌（ZnPc-（COOH）（8））（{Cu-8（ZnPc-（COOH）（8））}（n），ZPCN）组成的纳米金属有机骨架纳米颗粒。在暗循环中，ATP可将ZPCN中的Cu ~（2+）去除，形成Cu-ATP络合物。铜离子介导的芬顿反应可破坏复合物中的ATP，最终导致ATP耗竭，抑制细胞增殖，使细胞对PDT敏感。在光周期中，ZPCN可产生大量的细胞毒性活性氧，抑制肿瘤生长。这些结果表明，在低氧条件下通过PDT实现肿瘤治疗的新策略的潜在适用性。
Hypoxia in solid tumors hinders the efficacy of photodynamic therapy (PDT). The route of generation of adenosine triphosphate (ATP) in hypoxic tumor cells comprises ineffective glycolysis processes, but ATP is crucial for rapid and uncontrolled growth and division. ATP depletion would inhibit DNA replication and glutathione (GSH) biosynthesis, which could inhibit the proliferation of cells and make them sensitive to PDT treatment. In this context, a nanoscale metal-organic framework nanoparticle consisting of Cu2+ and carboxyl-modified zinc phthalocyanine (ZnPc-(COOH)(8)) ({Cu-8(ZnPc-(COOH)(8))}(n), ZPCN) was designed and prepared. In the dark cycle, ATP could remove Cu2+ from ZPCN and form a copper-ATP complex. ATP in the above complex could be destroyed by a copper-mediated Fenton reaction, which could finally induce ATP depletion to inhibit the proliferation of cells and make them sensitive to PDT treatment. In the light cycle, ZPCN could generate abundant cytotoxic reactive oxygen species to suppress tumor growth. These results demonstrated the potential applicability of the new strategy for achieving tumor treatment in hypoxic conditions by PDT.