Stable Synthetic Bacteriochlorins: Potent Light-Activated Anti-Cancer Drugs
Stable Synthetic Bacteriochlorins: Potent Light-Activated Anti-Cancer Drugs
复制标题
DOI：
10.2174/1385272819666150303233445
复制
发表时间：
2015-01-01
影响因子：
2.6
通讯作者：
Hamblin, Michael R.
中科院分区：
文献类型：
--
作者：
Huang, Ying-Ying;Luo, Dianzhong;Hamblin, Michael R.
光动力疗法（PDT）使用称为光敏剂（PS）的无毒染料以非热功率密度吸收可见或近红外波长的光，所述光（在氧存在下）联合收割机结合在一起以产生活性氧物质（ROS）。形成的主要ROS是单线态氧和羟基自由基，它们都具有细胞毒性作用。PDT具有两种独立的特异性机制，这是由于在肿瘤中的特异性积累加上空间受限的照明。第一代PS是卟啉，但由于需要长波长活化以提高组织渗透性，第二代二氢卟酚（远红）和细菌绿素（BC）（近红外[NIR]）已被研究。本文综述了定量结构-功能与电荷和亲脂性的关系，中心金属原子对确定光化学机制的影响，吸电子二氰基对防止光漂白的影响，胶束纳米载体时发现的活性改善，以及单取代对称双取代的相对优势。最后，长波长（730 nm）激活的必要性，强调通过在PDT的色素性黑色素瘤在体外和小鼠模型的黑色素瘤。
Photodynamic therapy (PDT) uses non-toxic dyes called photosensitizers (PS) to absorb light of visible or near-infrared wavelengths at non-thermal power densities that (in the presence of oxygen) combine together to produce reactive oxygen species (ROS). The main ROS formed are singlet oxygen and hydroxyl radicals that can both have cytotoxic effects. PDT has two separate mechanisms of specificity due to specific accumulation in the tumor coupled with spatially confined illumination. The first-generation PS were porphyrins, but due to the need for long-wavelength activation to improve tissue penetration, second-generation chlorins (far red) and bacteriochlorins (BC) (near infrared [NIR]) have been investigated. This review covers quantitative structure-function relationship with charge and lipophilicity, the effect the central metal atom has on determining the photochemical mechanism, the effect that electron withdrawing di-cyano groups have on preventing photobleaching, the improvement in activity found when micellar nanocarriers are employed, and the relative superiority of mono-substitution over symmetrical di-substitution. Finally, the necessity for long-wavelength (730 nm) activation is underlined by looking at PDT of pigmented melanoma in vitro and in a mouse model of melanoma.