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Principal Investigator: Colby Shad Thaxton
Organization: NORTHWESTERN UNIVERSITY AT CHICAGO
Fiscal Year: 2024
Award: $275,984
Funding agency: National Institute of Arthritis and Musculoskeletal and Skin Diseases
SUMMARY
The overall goal of the Lipid-Based Self-Assembled Materials and Characterization Core (LBSAMCC) is to
synthesize, characterize, and deliver highly novel therapeutics for ameliorating the devastating effects of nitrogen
and sulfur mustards to the eye (Project 1) and skin (Project 2). High-density lipoproteins (HDL) are small
nanoparticles that solubilize and transport cholesterol and lipids, are integral in modulating the innate immune
system, and function to enhance the integrity of epithelial barriers. The development and delivery of novel
materials that mimic these key functional features of HDLs and, importantly, enable targeting of appropriate cell
types (e.g. innate immune cells, keratocytes, and keratinocytes) in the eye and skin, highly differentiate this
platform from others to ameliorate injuries caused by mustards. The Thaxton lab pioneered the synthesis of
HDL-like synthetic biologics (HDL NPs) with an inert, solid core gold nanoparticle (AuNP) upon which the self-
assembly of lipid and protein cargos of HDLs can chemically attach. The overall size and surface chemistry can
be strictly controlled to resemble native HDLs enabling these first-generation materials to be tailorable, such that
any number of phospholipids, sterols, and/ or small molecule drugs (e.g. siRNA or microRNA) may be added.
Recent collaborations between the Thaxton and Nguyen labs further demonstrated that the AuNP of first-
generation materials can be swapped out for size-controlling organic core (oc) scaffolds, which can be used to
control biological function (e.g. cholesterol uptake and anti-inflammatory) and opens up the opportunity to load
and unload the core of these targeted materials with relevant therapies (e.g. vitamin D). Ultimately, synthetic
HDL biologics offer a tremendous opportunity for developing novel therapies against eye and/or skin injuries that
occur due to exposure to mustards. The LBSAMCC will be directly responsible for synthesizing a suite of organic
cores (Specific Aim 1) to be used as templates to produce a library of ocHDL NPs with and without small-
molecule and lipid-conjugated drugs and formulated to be topically applied to the eye and skin (Specific Aim 2).
Furthermore, the LBSAMCC will facilitate the complete physicochemical and functional screening of the ocHDL
NPs (Specific Aim 3) so that they can be confidently delivered and further developed in each of the Projects. As
such, the LBSAMCC will deliver effective ocHDL NPs to remediate chemical mustard injuries to the eye and
skin. The impact of this work is that a rigorous approach and step-wise method will produce effective topically
delivered therapies for ameliorating the devastating injuries caused to the eye and skin by nitrogen and sulfur
mustard.
Terms: <Address><Affinity><Anti-Inflammatories><Anti-Inflammatory Agents><Anti-inflammatory><Apo A-1><Apo A-I><Apo A1><Apo AI><ApoA-1><ApoA-I><Apolipoprotein A-1><Apolipoprotein A-I><Apolipoprotein A1><Apolipoprotein AI><Binding><Biological><Biological Agent><Biological Function><Biological Process><Biological Products><Bis(beta-chloroethyl) Sulfide><Blood Serum><Calciol><Cell Body><Cell model><Cells><Cellular model><Chemicals><Chemistry><Chloramin><Chlorethazine><Chlormethine><Cholecalciferol><Cholesterol><Clinic><Collaborations><Cream><Data><Dermal injury><Development><Di-2-chloroethyl Sulfide><Diameter><Dichlorodiethyl Sulfide><Drug Delivery><Drug Delivery Systems><Drugs><Epithelial Cells><Epithelium><Exposure to><Eye><Eye Drops><Eye Injuries><Eyeball><Eyedrops><Formulation><Generations><Goals><Gold><H-bond><HDL><HDL Lipoproteins><HN-2><HN2><Heavy Lipoproteins><High Density Lipoproteins><High density lipoprotein><Hydrogen Bonding><Hydrophobicity><Imaging Procedures><Imaging Technics><Imaging Techniques><Immune><Immunes><In vivo analysis><Inflammation><Inflammatory><Infrastructure><Injury><Innate Immune System><Libraries><Lipids><Location><Mechlorethamine><Medication><Methods><Methylchlorethamine><Micro RNA><MicroRNAs><Molecular Interaction><Mustard><Mustard Gas><Mustine><Nitrogen Mustard><Nucleic Acids><Ocular Injury><Organic Synthesis><Pathway interactions><Peptides><Pharmaceutical Preparations><Phosphatides><Phospholipids><Process><Property><Proteins><Receptor Protein><Serum><Short interfering RNA><Skin><Skin injury><Small Interfering RNA><Solid><Sterols><Structure><Sulfur Mustard><Surface><Therapeutic><Topical Drug Administration><Topical application><Translations><Universities><VIT D><VitD3><Vitamin D><Vitamin D 3><Vitamin D3><Work><Wound Repair><Yellow Cross Liquid><Yperite><acetyl-LDL receptor><acetylated LDL receptor><administer topically><alpha-Lipoproteins><apply topically><arm><biologic><biologics><biopharmaceutical><biotherapeutic agent><cell imaging><cell type><cellular imaging><chloromethine><critical injury><cutaneous injury><deliver topically><devastating injury><developmental><drug release profile><drug/agent><epidermal injury><eye trauma><fat metabolism><flexibility><flexible><gold nano particle><gold nanoparticle><healing><hydrophilicity><in vivo><in vivo evaluation><in vivo testing><injuries><injuries to skin><keratinocyte><keratinocyte differentiation><lipid metabolism><miRNA><miRNAs><nano gold><nano particle><nano-sized particle><nanoGold><nanoparticle><nanosized particle><nanotherapeutic><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation therapeutics><novel><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><ocular trauma><pathway><receptor><remediation><scaffold><scaffolding><scavenger receptor><screening><screenings><self assembly><severe injury><siRNA><small molecule><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><technology platform><technology system><topical administration><topical delivery><topical drug application><topical treatment><topically administered><topically applied><topically delivered><topically treated><translation><treat topically><uptake><wound healing><wound recovery><wound resolution>