Light-controllable cell-membrane disturbance for intracellular delivery

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 c...

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Bibliographic Details
Published in:Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2024-05, Vol.12 (17), p.4138-4147
Main Authors: Huo, Wenting, Miki, Koji, Mu, Huiying, Osawa, Takashi, Yamaguma, Harumi, Kasahara, Yuuya, Obika, Satoshi, Kawaguchi, Yoshimasa, Hirose, Hisaaki, Futaki, Shiroh, Miyazaki, Yusuke, Shinoda, Wataru, Akai, Shuji, Ohe, Kouichi
Format: Article
Language:English
Subjects:
Cell membranes
Controllability
Cytoplasm
Endocytosis
Intracellular
Irradiation
Light
Light irradiation
Low temperature
Membranes
Molecular weight
Oligonucleotides
Peptides
Radiation
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Summary: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. A light-controllable delivery method based on the tetraphenylethene derivative was developed to improve the intracellular delivery of charged molecules. It does not require chemical modification of drugs and is applicable to a variety of cell lines.
ISSN:2050-750X
2050-7518
DOI:10.1039/d3tb02956e