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.
Keywords: aggregation-induced emission; autophagy; inhibitors; pyridinium-substituted tetraphenylethylenes; tumors.
© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.