Light-controllable cell-membrane disturbance for intracellular delivery

Area of Science:

• Biotechnology
• Materials Science
• Cell Biology

Background:

• Charged molecules like oligonucleotides struggle to cross cell membranes.
• Existing delivery methods often rely on endocytosis, which can be inefficient.

Purpose of the Study:

• To develop a novel method for light-triggered intracellular delivery of charged molecules.
• To investigate an endocytosis-independent delivery pathway using a twistable tetraphenylethene derivative.

Main Methods:

• Synthesis of a light-responsive tetraphenylethene (TPE) derivative, TPE-C-N.
• Utilizing light irradiation to induce a planar-to-twisted structural change in TPE-C-N.
• Assessing intracellular delivery efficiency under inhibited endocytosis conditions (low temperature).

Main Results:

• TPE-C-N demonstrated light-triggered cell membrane disturbances without causing permanent damage.
• Significantly enhanced intracellular delivery of negatively charged molecules (peptides, oligonucleotides) under light.
• Confirmed an endocytosis-independent delivery mechanism for molecules up to 5000 Da.

Conclusions:

• TPE-C-N provides an effective, light-controllable strategy for intracellular delivery of charged biomolecules.
• The endocytosis-independent pathway offers a promising alternative for drug and gene delivery.
• This technology has potential applications in delivering oligonucleotides and peptides for therapeutic purposes.