Rock the nucleus: significantly enhanced nuclear membrane permeability and gene transfection by plasmonic nanobubble induced nanomechanical transduction

Abstract

Efficient delivery to the cell nucleus remains a significant challenge for many biomolecules, including anticancer drugs, proteins and DNAs. Despite numerous attempts to improve nuclear import including the use of nuclear localization signal (NLS) peptides and nanoparticle carriers, they are limited by the nanoparticle size, conjugation method, dependence on the functional nuclear import and intracellular trafficking mechanisms. To overcome these limitations, here we report that the nanomechanical force from plasmonic nanobubbles increases nuclear membrane permeability and promotes universal uptake of macromolecules into the nucleus, including macromolecules that are larger than the nuclear pore complex and would otherwise not enter the nucleus. Importantly, we show that plasmonic nanobubble-induced nanomechanical transduction significantly improves gene transfection and protein expression, compared to standard electroporation treatment alone. This novel nanomechanical transduction increases the size range and is broadly applicable for macromolecule delivery to the cell nucleus, leading to new opportunities and applications including for gene therapy and anticancer drug delivery.