Laser-Activated Polymeric Microcapsules for Ultrasound Imaging and Therapy: In Vitro Feasibility

Abstract

Polymeric microcapsules with a light-absorbing dye incorporated in their shell can generate vapor microbubbles that can be spatiotemporally controlled by pulsed laser irradiation. These contrast agents of 6-8 μm in diameter can circulate through the vasculature, offering possibilities for ultrasound (molecular) imaging and targeted therapies. Here, we study the impact of such vapor bubbles on human endothelial cells in terms of cell poration and cell viability to establish the imaging and therapeutic windows. Two capsule formulations were used: the first one consisted of a high boiling point oil (hexadecane), whereas the second was loaded with a low boiling point oil (perfluoropentane). Poration probability was already 40% for the smallest bubbles that were formed (<7.5 μm diameter), and reached 100% for the larger bubbles. The hexadecane-loaded capsules also produced bubbles while their shell remained intact. These encapsulated bubbles could therefore be used for noninvasive ultrasound imaging after laser activation without inducing any cell damage. The controlled and localized cell destruction achieved by activation of both capsule formulations may provide an innovative approach for specifically inducing cell death in vivo, e.g., for cancer therapy.