A5060042802- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Lipid Membrane Structure and Behavior
- Dendrimers and Hyperbranched Polymers
- Cell Adhesion Molecules Research
- Heat shock proteins research
- Erythrocyte Function and Pathophysiology
- Signaling Pathways in Disease
- Coronary Interventions and Diagnostics
- 3D Printing in Biomedical Research
- Advanced Drug Delivery Systems
- Protein purification and stability
- Bone Tissue Engineering Materials
- Melanoma and MAPK Pathways
- Nuclear Receptors and Signaling
- Diagnosis and Treatment of Venous Diseases
- Neuroscience and Neural Engineering
- Synthesis and properties of polymers
- Tissue Engineering and Regenerative Medicine
- Cell death mechanisms and regulation
- Biochemical effects in animals
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Galectins and Cancer Biology
- Antimicrobial Peptides and Activities
- Innovative Microfluidic and Catalytic Techniques Innovation
Vanderbilt University
2013-2023
Quinnipiac University
2021
Vanderbilt University Medical Center
2016-2018
Virginia Innovation Partnership Corporation
2016
Center for Nanoscale Science and Technology
2013
Phospholipid bilayers that constitute endo-lysosomal vesicles can pose a barrier to delivery of biologic drugs intracellular targets. To overcome this barrier, number synthetic drug carriers have been engineered actively disrupt the endosomal membrane and deliver cargo into cytoplasm. Here, we describe hemolysis assay, which be used as rapid, high-throughput screen for cytocompatibility endosomolytic activity systems. In human red blood cells test materials are co-incubated in buffers at...
Endolysosome entrapment is one of the key barriers to therapeutic use biologic drugs that act intracellularly. The screening prospective nanoscale endosome-disrupting delivery technologies currently limited by methods are indirect and cumbersome. Here, we statistically validate Galectin 8 (Gal8) intracellular tracking as a superior approach direct, quantitative, predictive cargo bioactivity through in vitro high-throughput vivo validation. Gal8 cytosolically dispersed protein that, when...
Abstract Peptides and biologics provide unique opportunities to modulate intracellular targets not druggable by conventional small molecules. Most peptides are fused with cationic uptake moieties or formulated into nanoparticles facilitate delivery, but these systems typically lack potency due low and/or entrapment degradation in endolysosomal compartments. Because most delivery reagents comprise lipids polymers, there is a of specifically optimized deliver cargo. Herein, we demonstrate the...
The complexity of CRISPR machinery is a challenge to its application for nonviral in vivo therapeutic gene editing. Here, we demonstrate that proteins, regardless size or charge, efficiently load into porous silicon nanoparticles (PSiNPs). Optimizing the loading strategy yields formulations are ultrahigh loading─>40% cargo by volume─and highly active. Further tuning polymeric coating on loaded PSiNPs nanocomposites achieve colloidal stability under cryopreservation, endosome escape, and...
Nanopolyplexes formulated from a pH-responsive, endosomolytic polymer with peptide inhibitor of MAPKAP kinase 2 block inflammatory and migratory signaling in vascular smooth muscle cells prevent intimal hyperplasia human saphenous vein grafts.
A platform technology has been developed and tested for delivery of intracellular-acting peptides through electrostatically complexed nanoparticles, or nano-polyplexes, formulated from an anionic endosomolytic polymer cationic therapeutic peptides. This initially optimized two unique vasoactive peptides, a phosphomimetic heat shock protein 20 inhibitor MAPKAP kinase II, to prevent pathological vasoconstriction (i.e., vasospasm) in human vascular tissue. These inhibit promote vasorelaxation...
Phospholipid bilayers that constitute endo-lysosomal vesicles can pose a barrier to delivery of biologic drugs intracellular targets. To overcome this barrier, number synthetic drug carriers have been engineered actively disrupt the endosomal membrane and deliver cargo into cytoplasm. Here, we describe hemolysis assay, which be used as rapid, high-throughput screen for cytocompatibility endosomolytic activity systems. In human red blood cells test materials are co-incubated in buffers at...
A green synthesis method for the preparation of polyglycidol in buffer with a high degree control is presented. Polymerizations were conducted phosphate buffered saline (PBS) varying pH 3.8, 6.0, and 8.0 deionized water at temperatures 60, 80, 100 °C. Taking advantage catalytic reactivity between glycidol afforded novel polymerization technique facile systems semibranched architectures branching (DB) 0.24, which situates polymers purely linear (DB = 0) hyperbranched 0.56–0.63) systems. This...
Vascular procedures, such as stenting, angioplasty, and bypass grafting, often fail due to intimal hyperplasia (IH), wherein contractile vascular smooth muscle cells (VSMCs) dedifferentiate synthetic VSMCs, which are highly proliferative, migratory, fibrotic. Previous studies suggest MAPK-activated protein kinase 2 (MK2) inhibition may limit VSMC proliferation IH, although the molecular mechanism underlying observation remains unclear. We demonstrated here that MK2 blocked program of...
Rapid, facile, and noncovalent cell membrane modification with alkyl-grafted anionic polymers was sought as an approach to enhance intracellular delivery bioactivity of cationic peptides. We synthesized a library acrylic acid-based copolymers containing varying amounts amine-reactive pentafluorophenyl acrylate monomer followed by postpolymerization series alkyl amines afford precise control over the length density aliphatic side chains. This synthetic strategy enabled systematic...
Poly(lactic-co-glycolic acid) (PLGA) is widely used as a vehicle for delivery of pharmaceutically relevant payloads. PLGA readily fabricated nano- or microparticle (MP) matrix to load both hydrophobic and hydrophilic small molecular drugs well biomacromolecules such nucleic acids proteins. However, targeting payloads the cell cytosol often limited by MP entrapment degradation within acidic endolysosomes. Poly(propylacrylic (PPAA) polyelectrolyte polymer with membrane disruptive capability...
Abstract Hydrolytically degrading nano‐polyplexes (HDG‐NPs) that reverse charge through conversion of tertiary amines to carboxylic acids were investigated improve intracellular un‐packaging siRNA and target gene silencing compared a non‐degradable analog (non‐HDG‐NPs). Both NP types comprised reversible addition‐fragmentation chain‐transfer (RAFT) synthesized diblock copolymers poly(ethylene glycol) (PEG) corona‐forming block cationic for nucleic acid packaging incorporated butyl...
Subarachnoid hemorrhage (SAH) is associated with vasospasm that refractory to traditional vasodilators, and inhibition of after SAH remains a large unmet clinical need. causes changes in the phosphorylation state small heat shock proteins (HSPs), HSP20 HSP27, vasospastic vessels. In this study, levels HSP27 were manipulated using nanotechnology mimic intracellular phenotype SAH-induced vasospasm, effect manipulation was tested on vasomotor responses intact tissues. This work provides insight...
Objectives: Unregulated intraoperative distension of human saphenous vein (SV) graft leads to supraphysiologic luminal pressures and causes acute physiologic cellular injury the conduit. The effect on tissue viscoelasticity, a biophysical property critical successful graft, is not well described. In this investigation, we quantify loss viscoelasticity in SV deformed by compare results distended pressure-controlled fashion. Materials Methods: Unmanipulated porcine was used as control or...
Subarachnoid hemorrhages affect 30,000 people each year and accounts for between 1-7% of all strokes. Nearly 85% the time that hemorrhage occurs, it is due to a cerebral aneurysm leads delayed vasospasm stroke. Traditional vasodilators cannot be used because they will cause systemic hypotension leaving an unmet clinical need. HSPB1 small heat shock related protein modulates vasorelaxation, downregulated in vasospastic vessels, represents potential therapeutic modality treatment SAH-induced...