Evaluation of oxygen dependence on in vitro and in vivo cytotoxicity of photoimmunotherapy using IR-700-antibody conjugates.
Evaluation of oxygen dependence on in vitro and in vivo cytotoxicity of photoimmunotherapy using IR-700-antibody conjugates.
复制标题
使用IR-700-抗体结合物评估氧对体外和体内细胞毒性的依赖性。
DOI：
10.1016/j.freeradbiomed.2015.03.038
复制
发表时间：
2015-08
影响因子：
7.4
通讯作者：
Krishna MC
中科院分区：
文献类型：
--
作者：
Kishimoto S;Bernardo M;Saito K;Koyasu S;Mitchell JB;Choyke PL;Krishna MC
使用近红外吸收光敏酞菁染料IRDye 700 DX（IR 700）与帕尼单抗（Pan）等肿瘤靶向抗体偶联的光免疫疗法（PIT）已在体外研究和小鼠的几个临床前模型中显示出疗效，有望用于临床转化。PIT导致体外快速坏死细胞死亡和体内肿瘤缩小。用Pan-IR 700缀合物进行的光化学研究表明，该试剂可以支持单线态氧的产生，并且在暴露于近红外（NIR）光后还产生活性氧物质。此外，在使用A431细胞的体外研究中，单线态氧清除剂废除了PIT与Pan-IR 700的功效，而在暴露室中氧耗尽至不可检测的水平几乎完全抑制了PIT的细胞毒性。在PIT处理的动物中，荷瘤小鼠的存活时间延长，但在PIT之前使肿瘤短暂缺氧的小鼠没有从治疗中获益。这项研究的结果支持分子氧衍生的物种在由PIT引起的细胞死亡中的核心作用。
Photoimmunotherapy (PIT) using the near infrared-absorbing photosensitizing phthalocyanine dye, IRDye 700DX (IR700) conjugated with a tumor-targeting antibody such as Panitumumab (Pan) has shown efficacy in vitro studies and several pre-clinical models in mice with promise for clinical translation. PIT results in rapid necrotic cell death in vitro and tumor shrinkage in vivo. Photochemical studies with the Pan-IR700 conjugate showed that this agent can support generation of singlet oxygen and also generate reactive oxygen species after exposure to near infra-red (NIR) light. Moreover, in vitro studies using A431 cells, singlet oxygen scavengers abrogated the efficacy of PIT with Pan-IR700, while oxygen depletion to undetectable levels in an exposure chamber almost completely inhibited the cellular cytotoxicity of PIT. Survival of tumor bearing mice was prolonged in PIT treated animals but mice whose tumors were made transiently hypoxic prior to PIT had no benefit from the treatment. The results from this study support a central role for molecular oxygen derived species in cell death caused by PIT.