Bubble-based propulsion of engineered particles for drug delivery and immunotherapy

Abstract

Biological barriers, such as mucus and cellular endothelia, obstruct the transport of drugs to diseased tissues. In this talk, I will highlight our recent work to overcome these barriers using engineering particles that undergo bubble-based propulsion in response to ultrasound. I will focus on two innovations. First, I will share our collaborative effort to synthesize hydrophobically modified mesoporous silica nanoparticles (MSNs) stabilized with phospholipids that entrap hydrophobic drugs. When insonated with high-intensity focused ultrasound, the MSNs undergo cavitation to rapidly propel through dense media and release drugs. Second, I will share our effort to fabricate microparticles with arbitrary three-dimensional shapes using two-photon lithography. These microparticles are capable of entrapping air bubbles of a defined size, leading to their efficient, frequency-dependent propulsion when stimulated by ultrasound. By modifying the surfaces of these particles, they can robustly attach to epithelial cell layers and release small molecule drugs for extended durations. By way of outlook, I will discuss how these technologies have potential to stimulate immune cells against tumor progression and to abate inflammation in auto-immune diseases.