| Abstract: | 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. |
