Substitution Activated Precise Phototheranostics through Supramolecular Assembly of AIEgen and Calixarene
Substitution Activated Precise Phototheranostics through Supramolecular Assembly of AIEgen and Calixarene
复制标题
通过 AIEgen 和杯芳烃的超分子组装替代激活精确光治疗
DOI：
10.1021/jacs.0c06872
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发表时间：
2020-09-16
影响因子：
15
通讯作者：
Tang, Ben Zhong
中科院分区：
文献类型：
--
作者：
Feng, Hai-Tao;Li, Yuanyuan;Tang, Ben Zhong
光动力学疗法（PDT）是一种很有前途的非侵入性治疗技术，在临床前试验中引起了越来越多的兴趣。然而，从实验室到临床的转化经常遇到光敏剂（PS）的不良暗细胞毒性的问题。现在，这一挑战可以通过使用主客体策略的级联替代激活光治疗诊断来解决。通过静电络合吡啶功能化的四苯乙烯，即TPE-PHO，和水溶性杯芳烃，TPE-PHO的暗细胞毒性显着抑制。复合物的纳米组装体显示出增强的生物相容性，并在体外选择性地定位于细胞质。当TPE-PHO在肿瘤部位被4，4 '-联苯胺二盐酸盐从杯芳烃的空腔中竞争性地置换时，其在肿瘤组织中的暗细胞毒性和光活性被恢复以在光照射下提供有效的PDT功效。细胞成像的结果显示，TPE-PHO在级联超分子取代过程中经历了从细胞质到线粒体的易位以杀死癌细胞。成功地实施了体内肿瘤成像和治疗，以评估疗效。这种超分子策略避免了繁琐的分子合成，并开辟了一个新的地点，容易调整PS的行为。
Photodynamic therapy (PDT) is a promising noninvasive therapeutic technique and has attracted increasing interests in preclinical trials. However, the translation from laboratory to clinic often encounters the problem of undesired dark cytotoxicity of photosensitizers (PSs). Now, this challenge can be addressed by cascaded substitution activated phototheranostics using the host-guest strategy. Through electrostatical complexation of pyridinium-functionalized tetraphenyl-ethylene, namely, TPE-PHO, and water-soluble calixarene, the dark cytotoxicity of TPE-PHO is dramatically inhibited. The nanoassemblies of the complex show enhanced biocompatibility and selectively locate at the cytoplasm in vitro. When TPE-PHO is competitively displaced from the cavity of calixarene by 4,4'-benzidine dihydrochloride at the tumor site, its dark cytotoxicity and photoactivity in tumor tissue are restored to give efficient PDT efficacy under light irradiation. The result from cell imaging reveals that TPE-PHO undergoes translocation from cytoplasm to mitochondria to kill the cancer cells during the cascaded supramolecular substitution process. In vivo tumor imaging and therapy are successfully implemented to evaluate the curative effect. Such a supramolecular strategy avoids tedious molecular synthesis and opens a new venue to readily tune the PS behaviors.