Pyridinium‐Substituted Tetraphenylethylenes Functionalized with Alkyl Chains as Autophagy Modulators for Cancer Therapy.

Huang, Yanyan; You, Xue; Wang, Lingna; Zhang, Guanxin; Gui, Shilang; Jin, Yulong; Zhao, Rui; Zhang, Deqing

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.

CANCER treatment; AUTOPHAGY; CELL death; CANCER cells; MITOCHONDRIA; IN vivo studies

Angewandte Chemie, 2020, Vol 132, Issue 25, p10128

0044-8249

Academic Journal

10.1002/ange.202001906