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

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.

Silver nanoparticles affect bidirectional crosstalk between mitochondria and lysosomes in hemocyte subtypes of the oyster Crassostrea hongkongensis

“…Mitophagy was found in AgNP and Ag + exposure groups. The elevated overlapping degree between mitochondria and lysosomes has been widely used as a sensitive indicator of the induction of mitophagy, 82 which was not found in agranulocytes (Fig. 8B) but occurred in semigranulocytes (Fig.…”

Aggregation‐Induced Emission Luminogens for Mitochondria‐Targeted Cancer Therapy

“…[20] Some of us designed a group of pyridinium-substituted tetraphenylethylenes (PTPE 5-7) as autophagy modulators for cancer therapy (Figure 3a). [21] Besides self-assembling, PTPE 5-7 were found to form complexes with albumin. By monitoring the red emission from PTPE 5-7, the albumin complexes were observed to selectively enter cancer cells which is benefited from the high expression of albumin receptors on cancer cells.…”

“…The fact that autophagy is essential for cancer progression motivates the development of chemical autophagy modulators for cancer therapy [20] . Some of us designed a group of pyridinium‐substituted tetraphenylethylenes (PTPE 5 – 7 ) as autophagy modulators for cancer therapy (Figure 3a) [21] . Besides self‐assembling, PTPE 5 – 7 were found to form complexes with albumin.…”

Structure-guided discovery of a luminescent theranostic toolkit for living cancer cells and the imaging behavior effect

“…in living cells. [53][54][55][56] Moreover, previous studies have suggested that methoxy group played a key role in the interaction between several FDA-approved EGFR inhibitors (e.g. erlotinib, getinib, brigatinib and osimertinib) and EGFR.…”