- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Nanoparticle-Based Drug Delivery
- Nanoplatforms for cancer theranostics
- Virus-based gene therapy research
- DNA and Nucleic Acid Chemistry
- Immunotherapy and Immune Responses
- Chemokine receptors and signaling
- Polymer Surface Interaction Studies
- Dendrimers and Hyperbranched Polymers
- Polyamine Metabolism and Applications
- Pancreatic and Hepatic Oncology Research
- Hydrogels: synthesis, properties, applications
- Lipid Membrane Structure and Behavior
- MicroRNA in disease regulation
- Graphene and Nanomaterials Applications
- Cancer Research and Treatments
- Viral Infectious Diseases and Gene Expression in Insects
- Advanced Polymer Synthesis and Characterization
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Photodynamic Therapy Research Studies
- Cancer therapeutics and mechanisms
- Cannabis and Cannabinoid Research
- Acute Kidney Injury Research
- Mesoporous Materials and Catalysis
University of Nebraska Medical Center
2015-2024
Nebraska Medical Center
2017-2024
China Pharmaceutical University
2015-2019
Wayne State University
2006-2019
St. Luke's Hospital
2019
Radiation Oncology Associates
2019
Pharmaceutical Biotechnology (Czechia)
2019
State Key Laboratory of Natural Medicine
2017-2018
University of Nebraska–Lincoln
2015
The University of Texas Southwestern Medical Center
2013
Poor tumor penetration is a major challenge for the use of nanoparticles in anticancer therapy. Moreover, inability to reach hypoxic cells that are distant from blood vessels results inadequate exposure antitumor therapeutics and contributes development chemoresistance increased metastasis. In present study, we developed iRGD-modified simultaneous delivery photosensitizer indocyanine green (ICG) hypoxia-activated prodrug tirapazamine (TPZ). The loaded with ICG TPZ showed significantly...
Temperature-dependent uptake and release of small molecules within porous silica nanoparticles has been achieved by treatment preformed, thiol-functionalized micro-to-mesoporous (MSN) with pyridyl disulfide-terminated poly(N-isopropylacrylamide) (PNIPAM−S−S−Py). The resulting nanoparticle−polymer composites show fluorescein at room temperature (below the lower critical solution temperature, LCST, polymer) a low level leakage 38 °C (above <2% after 2 h). data are consistent mode action in...
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...
CXCR4 antagonistic nanocomplex regulates the immune process to enhance anti–PD-L1 immunotherapy.
Gene therapy for systemic diseases requires intravenous administration, but existing vectors are not suitable delivery, often showing rapid elimination from the bloodstream that restricts potential transfection sites to "first-pass" organs. To develop long-circulating vectors, here we have compared polyplexes containing DNA and poly-L-lysine (PLL) or polyethylenimine (PEI), surface-modified with either monovalent polyethylene glycol (PEG) multivalent copolymers of...
Synthetic vectors based on reducible polycations consisting of histidine and polylysine residues (HIS RPCs) were evaluated for their ability to deliver nucleic acids. Initial experiments showed that RPC-based with at least 70% content mediated efficient levels gene transfer without requirement the endosomolytic agent chloroquine. Significant was observed in a range cell types achieving up 5-fold increase percentage transfected cells compared 25 kDa PEI, gold standard synthetic vector. In...
Cationic polymer/DNA complexes are widely used for gene delivery, although the influence of cationic polymer on biophysical properties resulting complex is poorly understood. Here, several series polymers have been to evaluate structural parameters DNA complexes. Parameters studied included length side chain, charge type (primary versus tertiary and quaternary), molecular weight, spacing along backbone. with short chains (such as polyvinylamine) formed small complexes, resistant...
Target-specific DNA delivery requires vectors that combine stability in the biological milieu, receptor-mediated uptake into target cells, and intracellular activation to mediate transgene expression. This is achieved here using polymer-coated based on plasmid complexed with a reductively degradable polycation (RPC), designed for intercellular degradation. The RPC were prepared by oxidation of terminal cysteinyl thiol groups Cys(Lys)10Cys. complexes coated surface-cross-linked multivalent...
Nanomedicines achieve tumor-targeted delivery mainly through enhanced permeability and retention (EPR) effect following intravenous (IV) administration. Unfortunately, the EPR is severely compromised in pancreatic cancer due to hypovascularity dense desmoplastic stroma. Intraperitoneal (IP) administration may be an effective EPR-independent local approach target peritoneal tumors. Besides improved delivery, combination strategies are needed improve therapy by targeting both cells cellular...
This study introduces a novel cross-linking strategy capable of successfully stabilizing CaP nanoparticles and stimuli-responsive small interfering RNA (siRNA) release. We synthesized polysaccharide derivative thiolated hyaluronic acid (HA-SH), which was slightly modified but multifunctional developed smart redox-responsive delivery system. siRNA efficaciously condensed by calcium phosphate (CaP) via electrostatic interaction to form positively charged inner "core". Disulfide cross-linked HA...
Binding of serum proteins to polyelectrolyte gene delivery complexes is thought be an important factor limiting bloodstream circulation and restricting access target tissues. Protein binding can also inhibit transfection activity <i>in vitro</i>. In this study a multivalent reactive hydrophilic polymer has been used protein binding. This based on poly-[<i>N</i>-(2-hydroxypropyl)methacrylamide] (pHPMA) bearing pendent oligopeptide (Gly-Phe-Leu-Gly) side chains terminated in 4-nitrophenoxy...
Abstract Background Inefficient intracellular delivery of nucleic acids limits the therapeutic usefulness synthetic vectors such as poly(L‐lysine) (PLL)/DNA polyplexes. This article reports on characterisation a new type vector based linear reducible polycation (RPC) that can be cleaved by environment to facilitate release acids. Methods RPCs molecular weight (mwt) 45 and 187 kDa were prepared oxidative polycondensation peptide Cys‐Lys 10 ‐Cys used condense The stability RPC‐based polyplexes...
A series of reducible hyperbranched poly(amido amine)s (RHB) with high transfection efficiency were designed and synthesized as nonviral gene delivery vectors. The polycations by Michael addition copolymerization N,N-dimethylaminodipropylenetriamine (DMDPTA) two bisacrylamide monomers N,N′-hexamethylene (HMBA) N,N′-cystamine (CBA). density disulfide linkages in the polymers was tuned varying feed molar ratio monomers. results demonstrate that content RHB controls molecular weight polycation...