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My scientific journey around the elderly: How I went from bone to brain delivery

Dr. Patricia Mora-Raimundo (Israel Institute of Technology)
Monday, 19 February 2024 00:00

Place: conference room, IMDEA Nanociencia.

Abstract

Over the last 2 decades, nanotechnology has changed the concept of treatment for a variety of diseases, producing a huge impact regarding drug delivery. As an example of targeted disease, osteoporosis has devastating clinical and economic consequences. Nanomedicine offers new therapeutic capabilities, such as targeted gene and protein delivery that are unattainable using traditional therapeutic approaches. Among the available nanocarriers, mesoporous silica nanoparticles (MSNs) have attracted great attention for intracellular delivery of nucleic acids. During my PhD I evaluated the effectiveness of a new potential osteoporosis treatment based on MSNs. The proposed system was effective in delivering SOST siRNA and osteostatin, both biomolecules with osteogenic properties, through systemic injection to bone tissue, increasing osteogenic related genes expression and improving bone microarchitecture.
Once facing my next step during my scientific journey, I changed the focus of my research to a different degenerative disease, but under a more challenging environment, the brain. Neurodegenerative Diseases (ND) are considered a significant challenge for nanomedicine due to the difficulty of reaching the central nervous system (CNS). Overcoming the principal challenge of penetrating the brain involves crossing the Blood-Brain Barrier (BBB), which restricts most nanoparticles to cross at therapeutically relevant doses. Therefore, the development of an improved delivery system to achieve brain targeting and neuronal uptake is urgently needed. During my latest project we have developed a system able to cross the BBB and bring antibodies to the CNS to treat Parkinson disease, succeeding in improving motor skill capabilities of diseased mice.
While the results obtained were exciting, the number of particles needed to be injected was still considerably high. Therefore, my next research challenge is to improve in a greater manner the brain uptake of the nanoparticles. Inspired by the popular tale, “the pied piper of Hamelin”, who lures rats out of the town with the music produce by his magic pipe, I suggest letting music open the nanomedicines’ way into the brain. Since brain stimulation may increase its glucose demand, I aim to enhance the accumulation of glucose-modified nanoparticles in the brain through music exposure. For the first time, a synergy between music and targeted LNPs delivery will be determined. The demonstration of this synergy will provide a great alternative for enhancing ND treatments, being able to target different CNS diseases by modifying the particle payload.