Payton Martinez

All Publications

• Acoustically activatable liposomes as a translational nanotechnology for site-targeted drug delivery and noninvasive neuromodulation. Nature nanotechnology Purohit, M. P., Yu, B. J., Roy, K. S., Xiang, Y., Ewbank, S. N., Azadian, M. M., Hart, A. R., Muwanga, G. P., Martinez, P. J., Wang, J. B., Taoube, A. K., Markarian, E., Macedo, N., Kwan, A. K., Lopez, D. G., Airan, R. D. 2025

  Abstract

  Stimulus-responsive drug delivery nanotechnologies promise noninvasive activation of the right drug at the right place at the right time. However, these systems often incorporate non-validated pharmaceutical excipients and other features that limit their clinical translation. Here we engineer the responsiveness of liposomes to a pulsed, low-intensity ultrasound activating stimulus by incorporating a generally regarded as safe excipient that alters the acoustic properties of the liposome core medium. We show that this approach permits loading and ultrasound-induced release of four drugs in vitro. We then leverage this performance to enable drug-mediated noninvasive neuromodulation of each of the central and the peripheral nervous system in vivo. These acoustically activatable liposomes formulated with common and validated pharmaceutical excipients and production processes provide a versatile system for stimulus-responsive site-targeted drug delivery and noninvasive neuromodulation, with high clinical translation potential.

  View details for DOI 10.1038/s41565-025-01990-5

  View details for PubMedID 40826187

  View details for PubMedCentralID 7372945

• Effect of Microbubble Size, Composition, and Multiple Sonication Points on Sterile Inflammatory Response in Focused Ultrasound-Mediated Blood-Brain Barrier Opening. ACS biomaterials science & engineering Martinez, P. J., Song, J. J., Castillo, J. I., DeSisto, J., Song, K., Green, A. L., Borden, M. 2024

  Abstract

  Blood-brain barrier opening (BBBO) using focused ultrasound (FUS) and microbubbles (MBs) has emerged as a promising technique for delivering therapeutics to the brain. However, the influence of various FUS and MB parameters on BBBO and subsequent sterile inflammatory response (SIR) remains unclear. In this study, we investigated the effects of MB size and composition, as well as the number of FUS sonication points, on BBBO and SIR in an immunocompetent mouse model. Using MRI-guided MB + FUS, we targeted the striatum and assessed extravasation of an MRI contrast agent to assess BBBO and RNaseq to assess SIR. Our results revealed distinct effects of these parameters on BBBO and SIR. Specifically, at a matched microbubble volume dose (MVD), MB size did not affect the extent of BBBO, but smaller (1 mum diameter) MBs exhibited a lower classification of SIR than larger (3 or 5 mum diameter) MBs. Lipid-shelled microbubbles exhibited greater BBBO and a more pronounced SIR compared to albumin-shelled microbubbles, likely owing to the latter's poor in vivo stability. As expected, increasing the number of sonication points resulted in greater BBBO and SIR. Furthermore, correlation analysis revealed strong associations between passive cavitation detection measurements of harmonic and inertial MB echoes, BBBO, and the expression of SIR gene sets. Our findings highlight the critical role of MB and FUS parameters in modulating BBBO and subsequent SIR in the brain. These insights inform the development of targeted drug delivery strategies and the mitigation of adverse inflammatory reactions in neurological disorders.

  View details for DOI 10.1021/acsbiomaterials.4c00777

  View details for PubMedID 39497639