Targeted Therapeutics and Nanodevices
Silvia Muro
ICREA Research Professor
Lab members
Belén García Lareu, PhD
Marcelle Silva de Abreu, PhD
Maximilian Loeck, PhD Student
Jan Hasa, PhD Student
Lab contact
Institution
Our projects
Our research interest sits at the interface between molecular-cellular biology and nanotechnology-drug delivery. The lab studies the biological mechanisms ruling how our cells and tissues transport cargoes to precise destinations within our bodies, and then applies this knowledge toward the design of “biologically-controlled” nanodevices for improved delivery of therapeutic agents to specific disease sites. Our goal is to gain non-invasive, efficient, and specific access within the body and its cells, to enable effective treatments currently unavailable or suboptimal.
We have a strong interest in developing drug delivery systems to cross the linings that separate body and cellular compartments. For instance, neurodegenerative conditions remain largely untreatable because the vast majority of available pharmaceuticals and drug carriers under development fail to traverse the endothelial barrier that separates the bloodstream from the brain tissue. A particular example is that of novel biological therapeutics, which have demonstrated potential to manipulate disease targets far more precisely than small chemical counterparts. However, these large and fragile therapeutics fail to traverse both the blood-brain barrier and the membranes that separate the extracellular environment from the intracellular milieu of intended target cells. We have demonstrated that the ICAM-1 pathway enables transcytosis across vascular endothelial linings, helping delivery across the blood-brain barrier and also inside cells of various types, where modulation of the carrier vehicle can be optimize to deliver biomolecules to intracellular compartments such as the cytosol or the nucleus.
We are looking at these aspects using models for metabolic, neurodegenerative and cardiovascular syndromes to enable effective treatment of these life-threatening disorders and maladies characterized by these pathological traits.
Last publications
Manthe R, Loeck M, Bhowmick T, Solomon M, Muro S. Intertwined mechanisms define transport of anti-ICAM nanocarriers across the endothelium and brain delivery of a therapeutic enzyme. J Control Release, 324:181-193, 2020 doi.org/10.1016/j.jconrel.2020.05.009
Roki N, Tsinas Z, Salomon M, Bowers J, Getts R, Muro S. Unprecedently high targeting specific to lung ICAM-1 using 3DNA nanocarriers. J Control Release. 305:41-49, 2019 doi: 10.1016/j.jconrel.2019.05.021.
Marcos-Contreras OA, Brenner JS, Kiseleva RY, Zuluaga-Ramirez V, Greineder CR, Villa CH, Hood ED, Myerson JW, Muro S, Persidsky Y, Muzykantov VR. Combining vascular targeting and the local first pass provides 100-fold higher uptake of ICAM-1-targeted vs untargeted nanocarriers in the inflamed brain. J Control Release. 301:54-61, 2019 doi: 10.1016/j.jconrel.2019.03.008.
Manthe R, Rappaport J, Solomon M, Gugutkov D, Hildreth M, Velovolu V, Long Y, Marugan J, Zheng W, Muro S. δ-Tocopherol Effect on Endocytosis and its Combination with Enzyme Replacement Therapy for Lysosomal Disorders: a New Type of Drug Interaction? J Pharm Exp Ther. 379:823-833, 2019 doi: 10.1124/jpet.119.257345
Silvia Muro
ICREA Research Professor
Lab members
Belén García Lareu, PhD
Marcelle Silva de Abreu, PhD
Maximilian Loeck, PhD Student
Jan Hasa, PhD Student
Lab contact
Institution
Our projects
Our research interest sits at the interface between molecular-cellular biology and nanotechnology-drug delivery. The lab studies the biological mechanisms ruling how our cells and tissues transport cargoes to precise destinations within our bodies, and then applies this knowledge toward the design of “biologically-controlled” nanodevices for improved delivery of therapeutic agents to specific disease sites. Our goal is to gain non-invasive, efficient, and specific access within the body and its cells, to enable effective treatments currently unavailable or suboptimal.
We have a strong interest in developing drug delivery systems to cross the linings that separate body and cellular compartments. For instance, neurodegenerative conditions remain largely untreatable because the vast majority of available pharmaceuticals and drug carriers under development fail to traverse the endothelial barrier that separates the bloodstream from the brain tissue. A particular example is that of novel biological therapeutics, which have demonstrated potential to manipulate disease targets far more precisely than small chemical counterparts. However, these large and fragile therapeutics fail to traverse both the blood-brain barrier and the membranes that separate the extracellular environment from the intracellular milieu of intended target cells. We have demonstrated that the ICAM-1 pathway enables transcytosis across vascular endothelial linings, helping delivery across the blood-brain barrier and also inside cells of various types, where modulation of the carrier vehicle can be optimize to deliver biomolecules to intracellular compartments such as the cytosol or the nucleus.
We are looking at these aspects using models for metabolic, neurodegenerative and cardiovascular syndromes to enable effective treatment of these life-threatening disorders and maladies characterized by these pathological traits.
Last Publications
Manthe R, Loeck M, Bhowmick T, Solomon M, Muro S. Intertwined mechanisms define transport of anti-ICAM nanocarriers across the endothelium and brain delivery of a therapeutic enzyme. J Control Release, 324:181-193, 2020 doi.org/10.1016/j.jconrel.2020.05.009
Roki N, Tsinas Z, Salomon M, Bowers J, Getts R, Muro S. Unprecedently high targeting specific to lung ICAM-1 using 3DNA nanocarriers. J Control Release. 305:41-49, 2019 doi: 10.1016/j.jconrel.2019.05.021.
Marcos-Contreras OA, Brenner JS, Kiseleva RY, Zuluaga-Ramirez V, Greineder CR, Villa CH, Hood ED, Myerson JW, Muro S, Persidsky Y, Muzykantov VR. Combining vascular targeting and the local first pass provides 100-fold higher uptake of ICAM-1-targeted vs untargeted nanocarriers in the inflamed brain. J Control Release. 301:54-61, 2019 doi: 10.1016/j.jconrel.2019.03.008.
Manthe R, Rappaport J, Solomon M, Gugutkov D, Hildreth M, Velovolu V, Long Y, Marugan J, Zheng W, Muro S. δ-Tocopherol Effect on Endocytosis and its Combination with Enzyme Replacement Therapy for Lysosomal Disorders: a New Type of Drug Interaction? J Pharm Exp Ther. 379:823-833, 2019 doi: 10.1124/jpet.119.257345