Zinc(II) Metalated Porphyrins as Photothermogenic Photosensitizers for Cancer Photodynamic/Photothermal Synergistic Therapy
Zinc(II) Metalated Porphyrins as Photothermogenic Photosensitizers for Cancer Photodynamic/Photothermal Synergistic Therapy
复制标题
锌(II)金属化卟啉作为光热光敏剂用于癌症光动力/光热协同治疗
DOI：
10.1021/acsami.7b15583
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发表时间：
2018-01-10
影响因子：
9.5
通讯作者：
Dong, Xiaochen
中科院分区：
文献类型：
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作者：
Ding, Kaikai;Zhang, Yewei;Dong, Xiaochen
卟啉衍生物是第一代光敏剂，为了更好地治疗肿瘤，迫切需要设计一种具有良好水溶性、强近红外吸收的卟啉。本文合成了3个新的卟啉衍生物，5,10,15,20-四（3,4-二甲氧基苯基）卟啉（P1）， 5,10,15,20-四（3,4-二甲氧基苯基）锌卟啉（ZnP1）和5,15-二（3,4-二甲氧基苯基）-10,20-二（（4-甲氧基苯基）乙基）锌卟啉（ZnP2）。其中，ZnP2在近红外（NIR）区域的q波段最长、最强，具有最强的光捕获能力和最深的肿瘤组织穿透能力。采用纳米沉淀法制备了3种卟啉衍生物纳米颗粒，纳米颗粒通过增强渗透性和滞留性，表现出良好的水分散性和被动肿瘤靶向性。此外，这些NPs表现出光动力和光热效应。通过系统研究P1、ZnP1和ZnP2 NPs在体外对Hela细胞的单线态氧量子产率和细胞毒性，发现ZnP2的单线态氧量子产率最高（79%），其NPs的体外治疗效果最好。体内实验表明，ZnP2 NPs具有高光毒性、低暗毒性和良好的生物相容性，可作为有前途的光热致光敏剂用于癌症治疗。
Porphyrin derivatives are the first-generation photosensitizers, and to design a strong near-infrared (NIR)-absorbing porphyrin with good water solubility is highly desired for better therapeutic effect to treat tumors. Herein, three new porphyrin derivatives, 5,10,15,20-tetrakis(3,4-dimethoxyphenyl) porphyrin (P1), 5,10,15,20-tetrakis(3,4-dimethoxyphenyl) zinc porphyrin (ZnP1), and 5,15-bis(3,4-dimethoxyphenyl) -10,20-bis ( (4-methoxyphenyl) ethynyl) zinc porphyrin (ZnP2) have been synthesized. Among them, ZnP2 shows the longest and most intensive Q-bands in the near-infrared (NIR) region, as it endows the strongest light-harvesting capability and deepest tumor tissue penetration. The three porphyrin derivatives were prepared into nanoparticles (NPs) via nanoprecipitation method, and the NPs exhibit good water dispersibility and passive tumor-targeting property through enhanced permeability and retention effect. Furthermore, these NPs demonstrate both photodynamic and photothermal effects. Through a systematic study of the singlet oxygen quantum yield and cytotoxicity of P1, ZnP1, and ZnP2 NPs in vitro on Hela cells, it is found that ZnP2 shows the highest singlet oxygen quantum yield (79%), and its NPs show the best therapeutic efficacy in vitro. In vivo experiments disclosed that ZnP2 NPs present high phototoxicity, low dark toxicity, and excellent biocompatibility, and could be used as promising photothermogenic photosensitizer for cancer treatment.