Asymmetric polyplex-nanocapsules loaded with photosentisizer for light-assisted gene transfer

Inefficient intracellular gene delivery is still a limitation for the clinical translation of gene therapy. Recently, photochemical internalization (PCI) has emerged with the opportunity to overcome endo-lysosomal sequestration in gene delivery, which utilizes photosensitizer (PS) plus light generating reactive oxygen species (ROS) at sub-lethal level to facilitate intracellularly targeted drug delivery. In this work, asymmetric polyplex-nanocapsules were prepared based on the triblock copolymers of PEG-PCL-PEI by using the simple solvent-injection method. Subsequently, the hydrophobic PS was encapsulated in the hydrophobic layer of polyplex-nanocapsules through hydrophobic interaction. The results from agarose gel electrophoresis and fluorescence scanning spectroscopy show that DNA could be condensed effectively and the PS was encapsulated, resulting in the stable polyplex-nanocapsules. The obtained polyplex-nanocapsules were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS) measurements with the average size ranging from 200 to 280nm and the negatively charged surface. Importantly, these polyplex-nanocapsules can be uptaken by Hela cells, resulting in improved gene transfection efficiency in comparison with the case without laser treatment due to the assistance of PCI effect. This work demonstrates a promising strategy to build the light-assisted gene delivery system containing PS and transporting genes simultaneously in one platform.