A5075794128- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Nanoparticle-Based Drug Delivery
- Electrospun Nanofibers in Biomedical Applications
- Osteoarthritis Treatment and Mechanisms
- Nanoplatforms for cancer theranostics
- Angiogenesis and VEGF in Cancer
- Bone Tissue Engineering Materials
- Graphene and Nanomaterials Applications
- Dendrimers and Hyperbranched Polymers
- Optical Coherence Tomography Applications
- Lipid Membrane Structure and Behavior
- Peripheral Artery Disease Management
- 3D Printing in Biomedical Research
- Hydrogels: synthesis, properties, applications
- Total Knee Arthroplasty Outcomes
- Cellular transport and secretion
- Coronary Interventions and Diagnostics
- Cell Adhesion Molecules Research
- Tissue Engineering and Regenerative Medicine
- CRISPR and Genetic Engineering
- Photoacoustic and Ultrasonic Imaging
- PI3K/AKT/mTOR signaling in cancer
- Immunotherapy and Immune Responses
- interferon and immune responses
Vanderbilt University
2016-2025
Houston Forensic Science Center
2025
University of Florida
2021-2023
Stevenson University
2017
Nashville Oncology Associates
2014-2016
Vanderbilt University Medical Center
2016
VA Tennessee Valley Healthcare System
2016
Center for Nanoscale Science and Technology
2013
University of Washington
2008-2012
The Wallace H. Coulter Department of Biomedical Engineering
2004-2010
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 family of pH-responsive diblock polymers composed poly[(ethylene glycol)-b-[(2-(dimethylamino)ethyl methacrylate)-co-(butyl methacrylate)], PEG-(DMAEMA-co-BMA), was reversible addition-fragmentation chain transfer (RAFT) synthesized with 0-75 mol % BMA in the second polymer block. The relative mole DMAEMA and varied order to identify a that can be used formulate PEGylated, siRNA-loaded polyplex nanoparticles (NPs) an optimized balance cationic hydrophobic content NP core based on siRNA...
A combination of anionic and RAFT polymerization was used to synthesize an ABC triblock polymer poly[(propylenesulfide)-block-(N,N-dimethylacrylamide)-block-(N-isopropylacrylamide)] (PPS-b-PDMA-b-PNIPAAM) that forms physically cross-linked hydrogels when transitioned from ambient physiologic temperature incorporates mechanisms for reactive oxygen species (ROS) triggered degradation drug release. At (25 °C), PPS-b-PDMA-b-PNIPAAM assembled into 66 ± 32 nm micelles comprising a hydrophobic PPS...
Combination therapies consisting of multiple short therapeutic RNAs, such as small interfering RNA (siRNA) and microRNA (miRNA), have enormous potential in cancer treatment they can precisely silence a specific set oncogenes target disease-related pathways. However, clinical use siRNA/miRNA combinations is limited by the availability safe efficient systemic delivery systems with sufficient tumor penetrating endosomal escaping capabilities. This study reports on development multifunctional...
Porous, resorbable biomaterials can serve as temporary scaffolds that support cell infiltration, tissue formation, and remodeling of nonhealing skin wounds. Synthetic are less expensive to manufacture than biologic dressings achieve a broader range physiochemical properties, but opportunities remain tailor these materials for ideal host immune regenerative responses. Polyesters well-established class synthetic biomaterials; however, acidic degradation products released by their hydrolysis...
Transgenic mouse models are increasingly being used to investigate the functions of specific growth factors or matrix proteins design therapeutic strategies for controlling blood vessel growth. However, available methodologies evaluating angiogenesis and arteriogenesis in these limited by animal size, user subjectivity, power visualize three-dimensional networks, capability employ a vigorous quantitative analysis. In this study, we employed contrast-enhanced microcomputed tomography imaging...
Abstract Skeletal trauma and impaired skeletal healing is commonly associated with diminished vascularity. Hypoxia inducible factor alpha (HIF‐1) a key transcription responsible for activating angiogenic factors during development tissue repair. Small molecule inhibitors of the prolyl hydroxylase enzyme (PHD), degrading HIF‐1, have been shown to activate are effective in inducing angiogenesis. Here we examined effects several commercially available PHD on bone marrow mesenchymal stromal...
Abstract OPN is an ECM protein with diverse localization and functionality. The role of during fracture healing was examined using wildtype OPN−/− mice. Results showed that plays important in regulation angiogenesis, callus formation, mechanical strength early stages facilitates late stage bone remodeling organization. Introduction: Osteopontin (OPN) extracellular matrix (ECM) functionality has been reported to play a regulatory both angiogenesis osteoclastic remodeling, two vital processes...
Technologies to increase tissue vascularity are critically important the fields of engineering and cardiovascular medicine. Currently, limited technologies exist encourage angiogenesis arteriogenesis in a controlled manner. In present study, we describe an injectable release system consisting VEGF encapsulated poly(lactic- co-glycolic acid) (PLGA) nanoparticles (NPs). The majority was released gradually over 2–4 days from NPs as determined by ELISA kinetics experiment. An vitro aortic ring...
Macrophages represent an important therapeutic target, because their activity has been implicated in the progression of debilitating diseases such as cancer and atherosclerosis. In this work, we designed characterized pH-responsive polymeric micelles that were mannosylated using "click" chemistry to achieve CD206 (mannose receptor)-targeted siRNA delivery. is primarily expressed on macrophages dendritic cells upregulated tumor-associated macrophages, a potentially useful target for therapy....
A system is engineered for temporally controlled delivery of siRNA from biodegradable tissue regenerative scaffolds. Therapeutic application this approach to silence PHD2 promotes expression pro-angiogenic genes by HIF1α and enhanced scaffold vascularization in vivo. This technology provides a new standard efficient controllable gene silencing modulate host response within biomaterials. As service our authors readers, journal supporting information supplied the authors. Such materials are...
Although siRNA-based nanomedicines hold promise for cancer treatment, conventional siRNA–polymer complex (polyplex) nanocarrier systems have poor pharmacokinetics following intravenous delivery, hindering tumor accumulation. Here, we determined the impact of surface chemistry on in vivo and delivery siRNA polyplexes. A library diblock polymers was synthesized, all containing same pH-responsive, endosomolytic polyplex core-forming block but different corona blocks: 5 kDa (benchmark) 20 linear...
Abstract Small interfering RNA (siRNA) has significant potential to evolve into a new class of pharmaceutical inhibitors, but technologies that enable robust, tissue‐specific intracellular delivery must be developed before effective clinical translation can achieved. A pH‐responsive, smart polymeric nanoparticle (SPN) with matrix metalloproteinase (MMP)‐7‐dependent proximity‐activated targeting (PAT) is described here. The PAT‐SPN designed trigger cellular uptake and cytosolic siRNA once...
Clinical translation of therapies based on small interfering RNA (siRNA) is hampered by siRNA's comprehensively poor pharmacokinetic properties, which necessitate molecule modifications and complex delivery strategies. We sought an alternative approach to commonly used nanoparticle carriers leveraging the long-lived endogenous serum protein albumin as siRNA carrier. synthesized conjugated a diacyl lipid moiety (siRNA-L2), rapidly binds in situ. siRNA-L2, comparison with unmodified siRNA,...
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...
The high potential of siRNAs to silence oncogenic drivers remains largely untapped due the challenges tumor cell delivery. Here, divalent lipid-conjugated are optimized for in situ binding albumin improve pharmacokinetics and Systematic variation siRNA conjugate structure reveals that location linker branching site dictates tendency toward association versus self-assembly, while lipid hydrophobicity reversibility also contribute intracellular lead increases accumulation 12-fold orthotopic...
Protein-based vaccines have significant potential as infectious disease and anticancer therapeutics, but clinical impact has been limited in some applications by their inability to generate a coordinated cellular immune response. Here, pH-responsive carrier incorporating poly(propylacrylic acid) (PPAA) was evaluated test whether improved cytosolic delivery of protein antigen could enhance CD8+ cytotoxic lymphocyte generation prophylactic tumor vaccine responses. PPAA directly conjugated the...