Recent studies have demonstrated that micron-sized bubbles can be generated by using gas-stabilizing nanoparticles under reduced acoustic pressures. Due to their small particle size and high ultrasound responsiveness, these nanoparticles hold great potential in ultrasound theranostics for applications from molecular ultrasound imaging to drug/gene delivery and tumor ablation. However, the major limitation for these particles is their low biodegradation properties due to their hydrophobic surfaces needed for gas stabilization. Here we describe the synthesis of biodegradable gas stabilizing nanoparticles, for the first time, by carefully engineering the surfaces of mesoporous silica nanoparticles. We show that optimizing the hydrophobic coating and stabilizing layer are both crucial for achieving biodegradable nanoparticles with good gas stabilizing ability and, thus, high ultrasound responsiveness. Using a low amount of hydrophobic coating increases the biodegradation rate of the nanoparticles but results in poor ultrasound responsiveness. On the other hand, using a high amount of hydrophobic coating can improve the ultrasound responsiveness but slows down the biodegradation process. Interestingly, we found that albumin stabilized nanoparticles were degraded in the simulated body fluid much faster than the nanoparticles stabilized using amphiphilic polymers or lipids. We demonstrated that under optimized experimental conditions, albumin stabilized nanoparticles (50 nm) with very high acoustic activity completely degraded in a week in both in vitro and in vivo conditions. We also showed that these biodegradable nanoparticles could be stabilized using other protein sources such as fetal bovine serum, albumin from different sources, and human plasma. Finally, we showed the potential therapeutic use of these nanoparticles through successful nanoparticle-mediated tumor ablation in human xenograft models.

Biodegradable gas stabilizing nanoparticles for tumor ablation

ACS Fall 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.