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Pyridinium‐Substituted Tetraphenylethylenes Functionalized with Alkyl Chains as Autophagy Modulators for Cancer Therapy
Author(s) -
Huang Yanyan,
You Xue,
Wang Lingna,
Zhang Guanxin,
Gui Shilang,
Jin Yulong,
Zhao Rui,
Zhang Deqing
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202001906
Subject(s) - autophagy , pyridinium , mitophagy , mitochondrion , tetraphenylethylene , lysosome , autophagosome , alkyl , cancer , in vivo , cancer cell , chemistry , materials science , microbiology and biotechnology , biochemistry , medicine , biology , aggregation induced emission , organic chemistry , apoptosis , physics , quantum mechanics , fluorescence , enzyme
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.