Beijing National Laboratory for Molecular Sciences, CAS Key Laboratories of Organic Solids and Analytical Chemistry for Living Biosystems, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
School of Chemistry, University of Chinese Academy of Sciences, Beijing, 100049, China.
Angew Chem Int Ed Engl. 2020 Jun 15;59(25):10042-10051. doi: 10.1002/anie.202001906. Epub 2020 Apr 7.
Tuning autophagy in a controlled manner could facilitate cancer therapy but it remains challenging. Pyridinium-substituted tetraphenylethylene salts (PTPE 1-3), able to target mitochondria and disrupt autophagy after forming complexes with albumin, are reported. Mitochondrion affinity and autophagy-inducing activity are improved by prolonging the length of alkyl chains in PTPE 1-3. PTPE 1-3 demonstrate proautophagic activity and a mitophagy blockage effect. Failure of autophagosome-lysosome fusion in downstream autophagy flux results in cancer cell death. Moreover, fast formation of complexes of PTPE 1-3 with albumin in blood can facilitate biomimetic delivery and deep tumor penetration. Efficient tumor accumulation and effective tumor suppression are successfully demonstrated with in vitro and in vivo studies. PTPE 1-3 salts exhibit dual functionality: they target and image mitochondria because of aggregation-induced emission effects and they are promising for cancer therapy.
以可控的方式调节自噬可以促进癌症治疗，但这仍然具有挑战性。报告了能够靶向线粒体并在与白蛋白形成复合物后破坏自噬的吡啶取代的四苯乙烯盐（PTPE 1-3）。通过延长 PTPE 1-3 中烷基链的长度，可以提高线粒体亲和力和诱导自噬的活性。PTPE 1-3 表现出促进自噬的活性和阻断线粒体自噬的作用。下游自噬流中自噬体-溶酶体融合的失败导致癌细胞死亡。此外，PTPE 1-3 与白蛋白在血液中快速形成复合物有助于仿生传递和深入肿瘤渗透。通过体外和体内研究成功证明了有效的肿瘤积累和有效的肿瘤抑制。PTPE 1-3 盐具有双重功能：由于聚集诱导发射效应，它们可以靶向和成像线粒体，并且它们有望用于癌症治疗。
