A5009509285- Supramolecular Self-Assembly in Materials
- Advanced Polymer Synthesis and Characterization
- RNA Interference and Gene Delivery
- Chemical Synthesis and Analysis
- Advanced biosensing and bioanalysis techniques
- Synthetic Organic Chemistry Methods
- Click Chemistry and Applications
- Tuberculosis Research and Epidemiology
- Polydiacetylene-based materials and applications
- Polymer Surface Interaction Studies
- DNA and Nucleic Acid Chemistry
- Mycobacterium research and diagnosis
- Molecular spectroscopy and chirality
- Nanoparticle-Based Drug Delivery
- Ultrasound in Clinical Applications
- Crystallization and Solubility Studies
- Dendrimers and Hyperbranched Polymers
- Liquid Crystal Research Advancements
- biodegradable polymer synthesis and properties
- Viral-associated cancers and disorders
- Ultrasound and Hyperthermia Applications
- Synthesis and Properties of Aromatic Compounds
- Medical Imaging and Pathology Studies
- Surfactants and Colloidal Systems
- X-ray Diffraction in Crystallography
Northwestern University
2018-2024
International Institute for Nanotechnology
2019-2024
University of Washington
2024
University of Oslo
2023
University of Virginia
2001-2022
Engineering Systems (United States)
2022
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
2020-2021
Brenner Children's Hospital
2020
University of California, San Diego
2010-2020
University of Minnesota
2019
An enzyme-responsive, paclitaxel-loaded nanoparticle is described and assessed in vivo a human fibrosarcoma murine xenograft. This work represents proof-of-concept study demonstrating the utility of enzyme-responsive nanoscale drug carriers capable targeted accumulation retention tumor tissue response to overexpressed endogenous enzymes. The goal nanomedicine treat malignancies through selective therapeutics diseased tissue. Nanoparticles offer potential package large quantities cargo per...
Getting in shape: DNA-brush copolymer amphiphiles assemble into micelles with morphologies determined by selective interactions that allow manipulation of the magnitude steric and electrostatic repulsions micelle shells. Cylinder-to-sphere phase transitions occur when an input DNA sequence is added to (see picture). Detailed facts importance specialist readers are published as ”Supporting Information”. Such documents peer-reviewed, but not copy-edited or typeset. They made available...
Micelles were prepared from polymer-peptide block copolymer amphiphiles containing substrates for protein kinase A, phosphatase-1, and matrix metalloproteinases 2 9. We examine reversible switching of the morphology these micelles through a phosphorylation-dephosphorylation cycle study peptide-sequence directed changes in response to proteolysis. Furthermore, exceptional uniformity particles makes them amenable cryo-TEM reconstruction techniques lending insight into their internal structure.
A key to the pathogenic success of Mycobacterium tuberculosis (Mtb), causative agent tuberculosis, is capacity survive within host macrophages. Although several factors required for this survival have been identified, a comprehensive knowledge such and how they work together manipulate environment benefit bacterial are not well understood. To systematically identify Mtb intracellular growth, we screened an arrayed, non-redundant transposon mutant library by high-content imaging characterize...
In this paper we present in situ transmission electron microscopy of synthetic polymeric nanoparticles with emphasis on capturing motion a solvated, aqueous state. The studied were obtained from the direct polymerization Pt(II)-containing monomer. resulting structures provided sufficient contrast for facile imaging situ. We contend that technique will quickly become essential characterization analogous systems, especially where dynamics are interest solvated describe preparation micellar...
ConspectusIn this Account, we describe the organization of functional peptides as densely arrayed side chains on polymer scaffolds which introduce a new class material called poly(peptide). We two general classes poly(peptide): (1) Peptide–Polymer Amphiphiles (PPAs), consist block copolymers with dense grouping hydrophilic and connected to hydrophobic that drives micelle assembly, (2) Protein-like Polymers (PLPs), wherein peptide-brush polymers are composed from monomers, each containing...
Successful and selective inhibition of the cytosolic protein-protein interaction (PPI) between nuclear factor erythroid 2-related 2 (Nrf2) Kelch-like ECH-associating protein 1 (Keap1) can enhance antioxidant response, with potential for a therapeutic effect in range settings including neurodegenerative disease (ND). Small molecule inhibitors have been developed, yet many off-target effects, or are otherwise limited by poor cellular permeability. Peptide-based strategies also attempted to...
Herein, we describe a polymeric micellar nanoparticle capable of rendering nucleic acids resistant to nuclease digestion. This approach relies on utilizing DNA as the polar headgroup DNA-polymer amphiphile in order assemble well-defined, discrete nanoparticles. Dense packing micelle corona allows for hybridization complementary oligonucleotides while prohibiting enzymatic degradation. We demonstrate preparation, purification, and characterization nanoparticles, then their resistance...
Enzyme-directed assembly in vivo: A targeting strategy is demonstrated, which leads to an active accumulation of nanoparticles by virtue event specific endogenous, enzymatic biochemical signals associated with tumor tissue. The viability this approach examined through a proof-of-concept study showing enzyme-directed particle and human xenograft tumors mice following intravenous injection, the retention particles demonstrated within for extended periods time.
Abstract The discovery of peptide substrates for enzymes with exclusive, selective activities is a central goal in chemical biology. In this paper, we develop hybrid computational and biochemical method to rapidly optimize peptides specific, orthogonal functions. an iterative machine learning process by which experimental data deposited into mathematical algorithm that selects potential be tested experimentally. Once tested, the uses refine future selections. This repeated until suitable set...
We report aqueous-phase Ring-Opening Metathesis Polymerization-Induced Self-Assembly (ROMPISA) for forming well-defined micellar polymer nanoparticles at room temperature and high solids concentration (20 w/w%). This is achieved with a new polymerization initiator, in the form of water-soluble cationic Hoveyda-Grubbs second generation catalyst. reaction was used water to produce diblock copolymers from norbornenyl monomers, which then self-assemble into myriad nanostructure morphologies...
In this paper, we describe a method for the stabilization of low-boiling point (low-bp) perfluorocarbons (PFCs) at physiological temperatures by an amphiphilic triblock copolymer which can emulsify PFCs and be cross-linked. After UV-induced thiol–ene cross-linking, core PFC emulsion remains in liquid form even exceeding their boiling points. Critically, formulation permits vaporization rarefactional pressures relevant clinical ultrasound.
Amphiphilic triblock copolymers containing Fe III ‐catecholate complexes formulated as spherical‐ or cylindrical‐shaped micellar nanoparticles ( SMN and CMN , respectively) are described new T 1 ‐weighted agents with high relaxivity, low cytotoxicity, long‐term stability in biological fluids. Relaxivities of both exceed those established gadolinium chelates across a wide range magnetic field strengths. Interestingly, shape‐dependent behavior is observed terms the particles' interactions HeLa...
We describe the design, synthesis, and antitumor activity of an 18 carbon α,ω-dicarboxylic acid monoconjugated via ester linkage to paclitaxel (PTX). This 1,18-octadecanedioic acid-PTX (ODDA-PTX) prodrug readily forms a noncovalent complex with human serum albumin (HSA). Preservation terminal carboxylic moiety on ODDA-PTX enables binding HSA in same manner as native long-chain fatty acids (LCFAs), within hydrophobic pockets, maintaining favorable electrostatic contacts between ω-carboxylate...
Herein, we report the photoinitiated polymerization-induced self-assembly (photo-PISA) of spherical micelles consisting proapoptotic peptide-polymer amphiphiles. The one-pot synthetic approach yielded micellar nanoparticles at high concentrations and scale (150 mg mL-1 ) with tunable peptide loadings up to 48 wt. %. size was tuned by varying lengths hydrophobic hydrophilic building blocks. Critically, peptide-functionalized imbued "KLA" peptides (amino acid sequence: KLAKLAKKLAKLAK) two key...
Novel, responsive liposomes are introduced, assembled from DNA-programmed lipids allowing sequence selective manipulation of nanoscale morphology. Short, single-stranded DNA sequences form polar head groups conjugated to hydrophobic tails. The morphology the resulting lipid aggregates depends on sterics and electronics in and, therefore, is dependent hybridization state. programmability, specificity, reversibility switchable system demonstrated via dynamic light scattering, transmission...
Abstract Harnessing metal‐free photoinduced reversible‐deactivation radical polymerization (photo‐RDRP) in organic and aqueous phases, we report a synthetic approach to enzyme‐responsive pro‐apoptotic peptide brush polymers. Thermolysin‐responsive peptide‐based polymeric amphiphiles assembled into spherical micellar nanoparticles that undergo morphology transition worm‐like micelles upon enzyme‐triggered cleavage of coronal sidechains. Moreover, polypeptide brushes show enhanced cell uptake...
We report the synthesis of a degradable polyphosphoramidate via ring-opening metathesis polymerization (ROMP) with Grubbs initiator (IMesH2)(C5H5N)2(Cl)2Ru═CHPh. Controlled ROMP low ring strain diazaphosphepine-based cyclic olefin was achieved at temperatures to afford well-defined polymers that readily undergo degradation in acidic conditions cleavage acid-labile phosphoramidate linkages. The diazaphosphepine monomer compatible random and block copolymerizations phenyl oligo(ethylene...
Melanins are a family of heterogeneous biopolymers found ubiquitously across plant, animal, bacterial, and fungal kingdoms where they act variously as pigments radiation protection agents. There exist five multifunctional yet structurally biosynthetically incompletely understood varieties melanin: eumelanin, neuromelanin, pyomelanin, allomelanin, pheomelanin. Although eumelanin allomelanin have been the focus most studies to date, some research suggests that pheomelanin has better absorption...