Echogenic Chitosan Nanodroplets for Spatiotemporally Controlled Gene Delivery
1Department of Ultrasound Medicine, Laboratory of Ultrasound Molecular Imaging, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, People’s Republic of China
2Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People’s Republic of China
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.
KEYWORDS: Hydrophobically Modified Chitosan, Gene Carrier, Ultrasonic Gene Transfer, Acoustic Droplet Vaporization, Cavitation.