Publications by authors named "Joann Gu"

3 Publications

  • Page 1 of 1

Peptide conjugation enhances the cellular co-localization, but not endosomal escape, of modular poly(acrylamide-co-methacrylic acid) nanogels.

J Control Release 2021 01 27;329:1162-1171. Epub 2020 Oct 27.

Department of Biomedical Engineering, University of Texas, Austin, TX 78712, USA; McKetta Department of Chemical Engineering, University of Texas, Austin, TX 78712, USA; Institute for Biomaterials, Drug Delivery, and Regenerative Medicine University of Texas, Austin, TX 78705, USA; Department of Pediatrics, Dell Medical School, Austin, TX 78712, USA; Department of Surgery and Perioperative Care, Dell Medical School, Austin, TX 78712, USA; Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, University of Texas, Austin, TX 78712, USA. Electronic address:

Nanoparticles must recognize, adhere to, and/or traverse multiple barriers in sequence to achieve cytosolic drug delivery. New nanoparticles often exhibit a unique ability to cross a single barrier (i.e. the vasculature, cell membrane, or endosomal compartment), but fail to deliver an adequate dose to intracellular sites of action because they cannot traverse other biological barriers for which they were not optimized. Here, we developed poly(acrylamide-co-methacrylic acid) nanogels that were modified in a modular manner with bioactive peptides. This nanogel does not recognize target cells or disrupt endosomal vesicles in its unmodified state, but can incorporate peptides with molecular recognition or environmentally responsive properties. Nanogels were modified with up to 15 wt% peptide without significantly altering their size, surface charge, or stability in aqueous buffer. Nanogels modified with a colon cancer-targeting oligopeptide exhibited up to a 324% enhancement in co-localization with SW-48 colon cancer cells in vitro, while influencing nanogel uptake by fibroblasts and macrophages to a lesser extent. Nanogels modified with an endosome disrupting peptide failed to retain its native endosomolytic activity, when coupled either individually or in combination with the targeting peptide. Our results offer a proof-of-concept for modifying synthetic nanogels with a combination of peptides that address barriers to cytosolic delivery individually and in tandem. Our data further motivate the need to identify endosome disrupting moieties which retain their activity within poly(acidic) networks.
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http://dx.doi.org/10.1016/j.jconrel.2020.10.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904656PMC
January 2021

Optimization of Cationic Nanogel PEGylation to Achieve Mammalian Cytocompatibility with Limited Loss of Gram-Negative Bactericidal Activity.

Biomacromolecules 2020 04 2;21(4):1528-1538. Epub 2020 Apr 2.

The LaMontagne Center for Infectious Disease, Austin, Texas 78712, United States.

Tuning the composition of antimicrobial nanogels can significantly alter both nanogel cytotoxicity and antibacterial activity. This project investigated the extent to which PEGylation of cationic, hydrophobic nanogels altered their cytotoxicity and bactericidal activity. These biodegradable, cationic nanogels were synthesized by activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) emulsion polymerization with up to 13.9 wt % PEG (MW = 2000) MA, as verified by H NMR. Nanogel bactericidal activity was assessed against Gram-negative and and Gram-positive and by measuring membrane lysis with a LIVE/DEAD assay. and viability was further validated by measuring metabolic activity with a PrestoBlue assay and imaging bacteria stained with a LIVE/DEAD probe. All tested nanogels decreased the membrane integrity (0.5 mg/mL dose) for Gram-negative and , irrespective of the extent of PEGylation. PEGylation (13.9 wt %) increased the cytocompatibility of cationic nanogels toward RAW 264.7 murine macrophages and L929 murine fibroblasts by over 100-fold, relative to control nanogels. PEGylation (42.8 wt %) reduced nanogel uptake by 43% for macrophages and 63% for fibroblasts. Therefore, PEGylation reduced nanogel toxicity to mammalian cells without significantly compromising their bactericidal activity. These results facilitate future nanogel design for perturbing the growth of Gram-negative bacteria.
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http://dx.doi.org/10.1021/acs.biomac.0c00081DOI Listing
April 2020

Student award for outstanding research winner in the Ph.D. category for the 2017 society for biomaterials annual meeting and exposition, april 5-8, 2017, Minneapolis, Minnesota: Characterization of protein interactions with molecularly imprinted hydrogels that possess engineered affinity for high isoelectric point biomarkers.

J Biomed Mater Res A 2017 06 25;105(6):1565-1574. Epub 2017 Feb 25.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas.

Molecularly imprinted polymers (MIPs) with selective affinity for protein biomarkers could find extensive utility as environmentally robust, cost-efficient biomaterials for diagnostic and therapeutic applications. In order to develop recognitive, synthetic biomaterials for prohibitively expensive protein biomarkers, we have developed a molecular imprinting technique that utilizes structurally similar, analogue proteins. Hydrogel microparticles synthesized by molecular imprinting with trypsin, lysozyme, and cytochrome c possessed an increased affinity for alternate high isoelectric point biomarkers both in isolation and plasma-mimicking adsorption conditions. Imprinted and non-imprinted P(MAA-co-AAm-co-DEAEMA) microgels containing PMAO-PEGMA functionalized polycaprolactone nanoparticles were net-anionic, polydisperse, and irregularly shaped. MIPs and control non-imprinted polymers (NIPs) exhibited regions of Freundlich and BET isotherm adsorption behavior in a range of non-competitive protein solutions, where MIPs exhibited enhanced adsorption capacity in the Freundlich isotherm regions. In a competitive condition, imprinting with analogue templates (trypsin, lysozyme) increased the adsorption capacity of microgels for cytochrome c by 162% and 219%, respectively, as compared to a 122% increase provided by traditional bulk imprinting with cytochrome c. Our results suggest that molecular imprinting with analogue protein templates is a viable synthetic strategy for enhancing hydrogel-biomarker affinity and promoting specific protein adsorption behavior in biological fluids. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1565-1574, 2017.
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http://dx.doi.org/10.1002/jbm.a.36029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6103214PMC
June 2017
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