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两种可见光响应发光光可还原一氧化碳供体的治疗潜力:脂溶性驱动的增强细胞内化。

Therapeutic Potential of Two Visible Light Responsive Luminescent photoCORMs: Enhanced Cellular Internalization Driven by Lipophilicity.

机构信息

Department of Chemistry and Biochemistry , University of California, Santa Cruz , 1156 High Street , Santa Cruz , California 95064 , United States.

Department of Chemistry and Biochemistry , Florida International University , 11200 SW Eighth Street , Miami , Florida 33199 , United States.

出版信息

Inorg Chem. 2019 Nov 4;58(21):14522-14531. doi: 10.1021/acs.inorgchem.9b02121. Epub 2019 Sep 24.

DOI:10.1021/acs.inorgchem.9b02121
PMID:31550141
Abstract

Herein we report the synthesis, characterization, and cellular internalization properties of two visible-light active luminescent Mn-based photoCORMs. The enhanced membrane permeability of the photoactive Mn carbonyl complex (photoCORM) derived from a designed lipophilic ligand namely, Mn(CO)(Imdansyl)() () (where = a diazabutadiene-based ligand containing two highly lipophilic adamantyl motifs, Imdansyl = dansylimidazole) promoted rapid internalization within human colorectal adenocarcinoma (HT-29) cells compared to Mn(CO)(Imdansyl)() () (where = a diazabutadiene ligand bearing two hydrophilic 1,3,5-triazaadamantyl group). Colocalization experiments using membrane stain indicate different extents of localization of the two CO complexes within the cellular matrix. Visible-light triggered CO release from the lipophilic photoCORM induced caspase-3/7 activation on HT-29 cells, which was detected using confocal microscopy. The rapid accumulation of the lipophilic photoCORM in the cellular membrane resulted in more efficient CO-induced cell death compared to the hydrophilic analogue .

摘要

在这里,我们报告了两种可见光活性发光锰基光可控制呼吸化合物(photoCORM)的合成、表征和细胞内化性质。与基于二氮杂丁二烯的配体(含两个高度亲脂性金刚烷基的配体)[Mn(CO)(Imdansyl)()](CFSO)()(其中 = )相比,光活性 Mn 羰基配合物(photoCORM)的增强的膜通透性()(其中 = )促进了人结直肠腺癌细胞(HT-29)内的快速内化。用膜染色进行的共定位实验表明,两种 CO 配合物在细胞基质中的定位程度不同。亲脂性 photoCORM 释放可见光触发的 CO 导致 HT-29 细胞中 caspase-3/7 激活,这可以使用共聚焦显微镜检测到。亲脂性 photoCORM 在细胞膜中的快速积累导致更有效的 CO 诱导的细胞死亡,与亲水性类似物相比。

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