Title : Ultrasound responsive bioactive microbubbles for enhanced drug delivery
Abstract:
In recent years, enzyme powered micro/nanomotors have emerged as ideal platforms for realizing various biological applications due to their multifunctionality and specificity in operation under complex conditions. However, most motors developed so far suffer from issues pertaining to their integration with biological systems due to retention of their synthetic components. With an aim to design a ‘vanishing’ micromotor completely devoid of non-biological components, we present a design of a microbubble (MB) motor made entirely from the protein bovine serum albumin. Due to their unique dynamics under ultrasound, which include oscillations, microstreaming, and shell rupture, these bubbles are also being probed as targeted drug delivery agents in tumours, and neurodegenerative diseases. The major drawback of such studies, however, is that after bubble collapse, the drugs rely simply on passive diffusion to navigate towards the target site, resulting in drug loss and decreased uptake efficiency. To overcome this, in the present study, these MBs were made ‘active’ by decorating catalase enzymes on their surface. Such motors were found to undergo substrate concentration dependent enhanced diffusion, just like their synthetic counterparts. Interestingly, in presence of passive tracer particles, these MBs were able to transfer energy across a distance 100 times their body length and enhance the diffusions of the tracers as well. This successful demonstration of enhanced diffusion and controlled energy transfer by biofunctionalized MBs marks an important first step in the direction of bubble based targeted drug delivery and activity based enhanced drug diffusion. This advancement not only opens new avenues in active matter research but also lays the foundation for developing biocompatible carriers capable of targeted cargo transport in complex physiological environments, with minimal risk of triggering adverse biological responses.
