人工仿生氯负载体已显示出作为抗癌支架的有前景应用。重要的是，能在癌细胞内选择性地激活的刺激响应氯离子转运体以避免对正常健康细胞的不良毒性非常罕见。特别是，光响应系统由于其时空可控性、低毒性和高可调节性，有望在光动力疗法中具有更好的适用性。在本工作中，我们报告了基于甲基苯基链联、苯并咪唑基的单照明保护和双照明保护的光缄藏前载体2a、2b、3a和3b，以及基于苯并咪唑-2-胺的活性转运体1a-1d。在活性化合物中，三氟甲基基团的负载体1a显示出高效的离子输送活性（EC50 = 1.2 ± 0.2 μM）。详细的机制研究揭示了Cl-/NO3-反向转运作为主要的离子转运过程。有趣的是，发现双照明保护对于实现完全的“关-态”并可以通过外部光源激活是必要的。该前载体最终在MCF-7癌细胞内被激活以诱导光毒性细胞死亡。此期刊为©皇家化学学会拥有版权。

Artificial biomimetic chloride anionophores have shown promising applications as anticancer scaffolds. Importantly, stimuli-responsive chloride transporters that can be selectively activated inside the cancer cells to avoid undesired toxicity to normal, healthy cells are very rare. Particularly, light-responsive systems promise better applicability for photodynamic therapy because of their spatiotemporal controllability, low toxicity, and high tunability. Here, in this work, we report o-nitrobenzyl-linked, benzimidazole-based singly and doubly protected photocaged protransporters 2a, 2b, 3a, and 3b, respectively, and benzimidazole-2-amine-based active transporters 1a-1d. Among the active compounds, trifluoromethyl-based anionophore 1a showed efficient ion transport activity (EC50 = 1.2 ± 0.2 μM). Detailed mechanistic studies revealed Cl-/NO3- antiport as the main ion transport process. Interestingly, double protection with photocages was found to be necessary to achieve the complete "OFF-state" that could be activated by external light. The procarriers were eventually activated inside the MCF-7 cancer cells to induce phototoxic cell death.This journal is © The Royal Society of Chemistry.