Effective treatment of glioblastoma (GBM) is limited by the challenge of delivering therapeutics across the blood-brain barrier and into targeted regions of the brain. This project aims to optimize lipid nanoparticles (LNPs) for use within a focused ultrasound (FUS) and click-chemistry mediated delivery platform previously developed by the laboratory. In this system, FUS is used with functionalized microbubbles to introduce chemical “anchors” within a targeted region, which enables the uptake and accumulation of complementarily functionalized LNPs at the treatment site. This approach has been demonstrated in vitro and in peripheral tissues, but has not yet been applied to the brain. My project will focus on identifying LNP formulations and delivery conditions that maximize transfection efficiency in vivo by varying component molar ratios and formulation parameters such as mixing conditions, and potentially comparing routes of administration. Initial studies will use Cre recombinase mRNA as a reporter system to evaluate delivery, with the longer term goal of testing therapeutic cargo in murine models of GBM. Ultimately, this work has the potential to contribute to the development of a more efficient and spatially targeted platform for delivering gene-based therapeutics to the brain, with applications in glioblastoma and other neurological diseases.
Northeastern University
