Publications by authors named "Abhijeet K Venkataraman"

3 Publications

  • Page 1 of 1

Polymer Composition Primarily Determines the Protein Recognition Characteristics of Molecularly Imprinted Hydrogels.

J Mater Chem B 2020 09 22;8(34):7685-7695. Epub 2020 Jul 22.

Department of Biomedical Engineering, University of Texas, Austin, TX, 78712, USA.

Synthetic hydrogels with the ability to recognize and bind target proteins are useful for a number of applications, including biosensing and therapeutic agent delivery. One popular method for fabricating recognitive hydrogels is molecular imprinting. A long-standing hypothesis of the field is that these molecularly imprinted polymers (MIPs) retain the chemical and geometric profile of their protein template, resulting in subsequent ability to recognize the template in solution. Here, we systematically determined the influence of network composition, as well as the identity, amount, and extraction of imprinting templates, on the protein binding of MIPs. Network composition (i.e. the relative number of ionizable and hydrophobic groups) explained the extent of protein adsorption in all cases. The identity and amount of imprinting template, albeit a protein or synthetic polymer (PEG) of similar molecular weight, did not significantly influence the amount of protein bound. While the purification method influenced the extent of template adsorption, it did so by chemically modifying the network (acrylamide hydrolysis, increasing the acid content by up to 21%) and not by voiding occupied MIP pores. Therefore, our results indicate that material composition determines the extent to which MIPs bind template and non-template proteins.
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http://dx.doi.org/10.1039/D0TB01627FDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807727PMC
September 2020

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

Synthetic networks with tunable responsiveness, biodegradation, and molecular recognition for precision medicine applications.

Sci Adv 2019 09 27;5(9):eaax7946. Epub 2019 Sep 27.

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

Formulations and devices for precision medicine applications must be tunable and multiresponsive to treat heterogeneous patient populations in a calibrated and individual manner. We engineered modular poly(acrylamide-co-methacrylic acid) copolymers, cross-linked into multiresponsive nanogels with either a nondegradable or degradable disulfide cross-linker, that were customized via orthogonal chemistries to target biomarkers of an individual patient's disease or deliver multiple therapeutic modalities. Upon modification with functional small molecules, peptides, or proteins, these nanomaterials delivered methylene blue with environmental responsiveness, transduced visible light for photothermal therapy, acted as a functional enzyme, or promoted uptake by cells. In addition to quantifying the nanogels' composition, physicochemical characteristics, and cytotoxicity, we used a QCM-D method for characterizing nanomaterial degradation and a high-throughput assay for cellular uptake. In conclusion, we generated a tunable nanogel composition for precision medicine applications and new quantitative protocols for assessing the bioactivity of similar platforms.
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http://dx.doi.org/10.1126/sciadv.aax7946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764836PMC
September 2019
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