Laser-induced vapor nanobubbles for efficient delivery of macromolecules in live cells

Macromolecular agents such as nucleic acids and proteins need to be delivered into living cells for therapeutic purposes. Among physical methods to deliver macromolecules across the cell membrane, laser- induced photoporation using plasmonic nanoparticles is a method that is receiving increasing attention in recent years. By irradiating gold nanoparticles bound to the cell membrane with laser light, nanosized membrane pores can be created. Pores are formed by localized heating or by vapour nanobubbles (VNBs) depending on the incident laser energy. Macromolecules in the surrounding cell medium can then diffuse through the transiently formed pores into the cytoplasm. While both heating and VNBs have been reported before for permeabilization of the cell membrane, it remains unclear which of both methods is more efficient in terms of cell loading with minimal cytotoxicity. In this study we report that under condition of a single 7 ns laser pulse VNBs are substantially more efficient for the cytosolic delivery of macromolecules. We conclude that VNB formation is an interesting photoporation mechanism for fast and efficient macromolecular delivery in live cells