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Light-controllable cell-membrane disturbance for intracellular delivery.

Wenting HuoKoji MikiHuiying MuTakashi OsawaHarumi YamagumaYusuke TamenoriSatoshi ObikaYoshimasa KawaguchiHisaaki HiroseShiroh FutakiYusuke MiyazakiWataru ShinodaShuji AkaiKouichi Ohe
Published in: Journal of materials chemistry. B (2024)
Highly polar and charged molecules, such as oligonucleotides, face significant barriers in crossing the cell membrane to access the cytoplasm. To address this problem, we developed a light-triggered twistable tetraphenylethene (TPE) derivative, TPE-C-N, to facilitate the intracellular delivery of charged molecules through an endocytosis-independent pathway. The central double bond of TPE in TPE-C-N is planar in the ground state but becomes twisted in the excited state. Under light irradiation, this planar-to-twisted structural change induces continuous cell membrane disturbances. Such disturbance does not lead to permanent damage to the cell membrane. TPE-C-N significantly enhanced the intracellular delivery of negatively charged molecules under light irradiation when endocytosis was inhibited through low-temperature treatment, confirming the endocytosis-independent nature of this delivery method. We have successfully demonstrated that the TPE-C-N-mediated light-controllable method can efficiently promote the intracellular delivery of charged molecules, such as peptides and oligonucleotides, with molecular weights ranging from 1000 to 5000 Da.
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