Antibody-targeted photolysis: in vitro immunological, photophysical, and cytotoxic properties of monoclonal antibody-dextran-Sn(IV) chlorin e6 immunoconjugates.
Antibody-targeted photolysis: in vitro immunological, photophysical, and cytotoxic properties of monoclonal antibody-dextran-Sn(IV) chlorin e6 immunoconjugates.
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抗体靶向光解：单克隆抗体-葡聚糖-Sn(IV) 二氢卟酚 e6 免疫缀合物的体外免疫学、光物理和细胞毒性特性。
DOI：
10.1021/bp00013a006
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发表时间：
1992
影响因子：
2.9
通讯作者：
Yarmush,ML
中科院分区：
文献类型：
--
作者：
Rakestraw,SL;Ford,WE;Tompkins,RG;Rodgers,MA;Thorpe,WP;Yarmush,ML
制备一组抗黑素瘤免疫缀合物，其含有18.9：1、11.2：1、6.8：1和1.7：1的氯6：抗体摩尔比。所有免疫缀合物保留抗原结合活性，而不管所获得的发色团：抗体取代比。相比之下，免疫缀合物的基态吸收光谱显示出似乎依赖于发色团：抗体摩尔比的特征。此外，观察到由共轭发色团产生的单线态氧的量子产率显著小于用未结合染料观察到的量子产率。发色团激发三重态的时间分辨吸收光谱表明，单线态氧量子产率的损失是由于发色团三重态产率的降低。从靶黑素瘤细胞的体外光解中获得的数据的分析，结合从免疫化学和光化学研究中获得的数据，表明观察到的免疫缀合物光毒性可以合理地定量表示为（1）免疫缀合物结合SK-MEL-2细胞表面抗原的能力，（2）通过免疫缀合物结合定位在靶细胞处的发色团的量，（3）在634 nm处的光的递送剂量，和（4）抗体结合的光敏剂的单线态氧量子产率。虽然这些数据强烈主张通过细胞膜处单线态氧的累积剂量进行光解，但是，不应排除同时光诱导释放其他细胞毒性剂。
A set of anti‐melanoma immunoconjugates were prepared which contained chlorine6: antibody molar ratios of 18.9:1, 11.2:1, 6.8:1, and 1.7:1. All immunoconjugates retained antigen binding activity regardless of the chromophore:antibody substitution ratio that was attained. In contrast, the ground‐state absorption spectra of the immunoconjugates showed features which appeared to be dependent on the chromophore: antibody molar ratio. In addition, the quantum yield of singlet oxygen generated by the conjugated chromophores was observed to be significantly less than that observed with the unbound dye. Time‐resolved absorbance spectroscopy of the chromophore excited triplet state indicated that the loss of singlet oxygen quantum yield resulted from diminished chromophore triplet yield. Analysis of data obtained from in vitro photolysis of target melanoma cells, in combination with that obtained from the immunochemical and photochemical studies, indicates that the observed immunoconjugate phototoxicity can be reasonably quantitatively represented by (1) the ability of the immunoconjugate to bind SK‐MEL‐2 cell surface antigen, (2) the amount of chromophore localized at the target cells by immunoconjugate binding, (3) the delivered dose of light at 634 nm, and (4) the singlet oxygen quantum yield of the antibody‐bound photosensitizer. Though these data argue strongly for photolysis by the cumulative dosage of singlet oxygen at the cell membrane, nonetheless, the concurrent photoinduced release of other cytotoxic agents should not be ruled out.