Echogenic Chitosan Nanodroplets for Spatiotemporally Controlled Gene Delivery

To attain attractive ultrasound-responsive gene delivery, a new kind of echogenic chitosan nanodroplets (CND) was developed to explore the potential to deliver genes in a spatiotemporally controlled manner. Self-assembled amphiphilic chitosan micelles of nanoscale size were fabricated to encapsulate hydrophobic perfluoropentane into the inner cores. The resulting CND presented a positive surface charge, enabling the formation of nano-complexes with genetic cargo through electrostatic interactions. Agarose-gel electrophoresis further confirmed the ability of CND to bind DNA. CND was also observed to protect DNA from degradation by nucleases. A temperature-dependent droplet-to-bubble conversion was also demonstrated. More importantly, our study revealed that CND in combination with ultrasound could significantly enhance gene delivery. In conclusion, our study demonstrated a novel carrier with great potential for efficient ultrasound-mediated gene delivery to specific tissues in a spatiotemporally controlled manner.