Silvia Muro

Associate Research Professor

Muro Group

Contact

Email: muro@umd.edu

Call: (301) 405-4777

Education

  • Ph.D., Molecular Biology, Universidad Autónoma de Madrid, Spain, 1999
  • B.S., Biology, Universidad de Granada, Spain, 1995

Profile

Dr. Silvia Muro’s research focuses on how molecules are transported within cells using intracellular transport systems, and applications of this research are being used to develop controlled delivery of therapeutics to precise disease targets.

Targeted delivery of therapeutic compounds is critical to improving the effectiveness of drugs and reducing undesirable side effects. Currently, most therapeutics do not have the ability to specifically target tissues or cells and, as a result, they are rapidly cleared from the body and are less effective. 

Subcellular distribution of cargo. (Left) Scheme and microscopy showing that fluorescent dextran delivered to cells via targeted polymer nanoparticles resides in vesicular compartments (bright red spots) around the cell nucleus (blue). (Right) Instead, dextran can escape vesicular compartments and reach the cytosol (more diffuse red color) when delivered using targeted “nucleodendrimers” (DNA-built dendrimers). Adapted from Muro (2014) Adv Funct Mat, 24(19):2899-2906.
Endocytosis and lysosomal trafficking of therapeutic carriers in mouse lungs. (Top) Polymer nanocarriers (NCs) bearing therapeutic acid sphingomyelinase (ASM) and targeted to ICAM-1 were observed by fluorescent microscopy to reach the lungs 30 min after i.v. injection in mice (green spots). (Bottom) Transmission electron microscopy of lungs collected 3 h after i.v. administration confirmed the presence of NCs (green) interacting with lung endothelial cells (ECs). For instance, NCs can be seen being engulfed by cells (black arrows), within cell endosomes (white arrowheads) and lysosomes (black arrowheads), and into subjacent epithelial cells (white arrow). VL = vessel lumen. Cv = caveolar vesicles. Cl = clathrin vesicles. Cj = cell junction. Scale bars = 300 nm. Reproduced from Garnacho et al. (2017) Mol. Ther. 25(7):1686-1696

Therapeutic molecules can be modified for improved targeting by attaching them to nanoscale carrier molecules like antibodies, peptides, or nanoparticles. These modifications allow therapeutic molecules to enter specific cells through the endocytic vesicular transport system and can improve the delivery of therapeutic agents within cells and across cellular layers of tissues or organs.

CURRENT RESEARCH

Dr. Muro’s lab works to understand how cells interact with and react to these nanoscale drug delivery carriers in order to optimize transport within the body and improve the therapeutic potential of the associated drug. The lab is focusing on two particularly challenging but therapeutically critical areas:  Improving transport across cellular linings (the blood-brain barrier and the gastrointestinal epithelium of the gut), as well as transport into intracellular compartments (lysosomes or the cytosol). While most drug delivery efforts aim to achieve this by focusing on carrier physicochemical optimization, the Muro lab aims to understand how these systems are sensed/transported in the body to impart “biological control” over their performance.

This research, between cell biology and drug delivery, provides a new complementary avenue where biological knowledge is used to optimize therapeutic nanotools. These platforms are being tested for the safe and efficient delivery of molecular probes,
drugs, enzymes, and nucleic acids for uses as analytical, diagnostic, and therapeutic tools, including in collaboration with industrial partners
(Genisphere, LLC).

Dr. Muro’s group is applying this technology toward engineering targeted nanocarriers and fusion proteins for the delivery of enzyme replacement therapies. These carriers are useful for the delivery of lysosomal enzymes that are deficient in life-threatening genetic diseases like lysosomal storage disorders. The group is also using nanocarriers as basic cell biology research tools to better understand pathways that regulate molecular transport, are exploited by pathogens, or are involved in immune responses.

Dr. Muro also leads the Targeted Therapeutic and Nanodevices group in IBEC, Barcelona, a sister lab focusing on complementary technologies to provide synergistic value to her research and training activities, and an international frame for extended impact.

Publications
2021
Drug Delivery Systems: A Few Examples of Applications, Drug Cargoes, and Administration Routes.
A method to improve quantitative radiotracing-based analysis of the in vivo biodistribution of drug carriers.
Engineering subtilisin proteases that specifically degrade active RAS.
Intracellular Delivery of Active Proteins by Polyphosphazene Polymers.
2020
Intertwined mechanisms define transport of anti-ICAM nanocarriers across the endothelium and brain delivery of a therapeutic enzyme.
2019
Alterations in Cellular Processes Involving Vesicular Trafficking and Implications in Drug Delivery.
δ-Tocopherol Effect on Endocytosis and Its Combination with Enzyme Replacement Therapy for Lysosomal Disorders: A New Type of Drug Interaction?
Unprecedently high targeting specificity toward lung ICAM-1 using 3DNA nanocarriers.
Combining vascular targeting and the local first pass provides 100-fold higher uptake of ICAM-1-targeted vs untargeted nanocarriers in the inflamed brain.
2018
Targeting superoxide dismutase to endothelial caveolae profoundly alleviates inflammation caused by endotoxin.
2017
Co-coating of receptor-targeted drug nanocarriers with anti-phagocytic moieties enhances specific tissue uptake versus non-specific phagocytic clearance.
ICAM-1-Targeted Nanocarriers Attenuate Endothelial Release of Soluble ICAM-1, an Inflammatory Regulator.
ICAM-1 targeting, intracellular trafficking, and functional activity of polymer nanocarriers coated with a fibrinogen-derived peptide for lysosomal enzyme replacement.
Enhanced Delivery and Effects of Acid Sphingomyelinase by ICAM-1-Targeted Nanocarriers in Type B Niemann-Pick Disease Mice.
Biodegradable "Smart" Polyphosphazenes with Intrinsic Multifunctionality as Intracellular Protein Delivery Vehicles.
Lysosomal enzyme replacement therapies: Historical development, clinical outcomes, and future perspectives.
2016
How Carrier Size and Valency Modulate Receptor-Mediated Signaling: Understanding the Link between Binding and Endocytosis of ICAM-1-Targeted Carriers.
Induced Pluripotent Stem Cells for Disease Modeling and Evaluation of Therapeutics for Niemann-Pick Disease Type A.
Intra- and trans-cellular delivery of enzymes by direct conjugation with non-multivalent anti-ICAM molecules.
Chitosan-Alginate Microcapsules Provide Gastric Protection and Intestinal Release of ICAM-1-Targeting Nanocarriers, Enabling GI Targeting In Vivo.