Publications by authors named "Hyukjun Choi"

Aggressive tumor formation often leads to excessive anaerobic glycolysis and massive production and accumulation of lactate in the tumor microenvironment (TME). To significantly curb lactate accumulation in TME, in this study, lactate oxidase (LOX) was used as a potential therapeutic enzyme and signal regulatory protein α variant (vSIRPα) as a tumor cell targeting ligand. SpyCatcher protein and SpyTag peptide were genetically fused to LOX and vSIRPα, respectively, to form SC-LOX and ST-vSIRPα and tumor-targeting LOX/vSIRPα conjugates were constructed via a SpyCatcher/SpyTag protein ligation system.

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Article Synopsis
  • Tumor cells need a lot of glucose and produce lactate through anaerobic glycolysis, creating a unique environment that helps them grow and evade the immune system.
  • To manage lactate levels in this tumor microenvironment (TME), researchers designed protein nanoparticles with lactate oxidase (LOX) and catalase (CAT) to break down lactate effectively.
  • The combination of LOX and CAT in these nanoparticles showed promising results in reducing tumor growth and modulating the TME by favoring immune cells that fight tumors, while minimizing harmful effects in a study on mice.
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The pandemic of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a public health emergency, and research on the development of various types of vaccines is rapidly progressing at an unprecedented development speed internationally. Some vaccines have already been approved for emergency use and are being supplied to people around the world, but there are still many ongoing efforts to create new vaccines. Virus-like particles (VLPs) enable the construction of promising platforms in the field of vaccine development.

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Peptides are gaining substantial attention as therapeutics for human diseases. However, they have limitations such as low bioavailability and poor pharmacokinetics. Periostin, a matricellular protein, can stimulate the repair of ischemic tissues by promoting angiogenesis.

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Protein cage nanoparticles have a unique spherical hollow structure that provides a modifiable interior space and an exterior surface. For full application, it is desirable to utilize both the interior space and the exterior surface simultaneously with two different functionalities in a well-combined way. Here, we genetically engineered encapsulin protein cage nanoparticles (Encap) as modular nanoplatforms by introducing a split-C-intein (Int) fragment and SpyTag into the interior and exterior surfaces, respectively.

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Magnetic resonance imaging (MRI) is a non-invasive in vivo imaging tool, providing high enough spatial resolution to obtain both the anatomical and the physiological information of patients. However, MRI generally suffers from relatively low sensitivity often requiring the aid of contrast agents (CA) to enhance the contrast of vessels and/or the tissues of interest from the background. The targeted delivery of diagnostic probes to the specific lesion is a powerful approach for early diagnosis and signal enhancement leading to the effective treatment of various diseases.

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In general immunoassays, secondary antibodies are covalently linked with enzymes and bind to the Fc region of target-bound primary antibodies to amplify signals of low-abundant target molecules. The antibodies themselves are obtained from large mammals and are further modified with enzymes. In this study, we developed novel recombinant immunoglobulin G (IgG)-binding luciferase-based signal amplifiers (rILSAs) by genetically fusing luciferase (Nluc) with antimouse IgG1 nanobody (MG1Nb) and antibody-binding domain (ABD), individually or together, in a mix-and-match manner.

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Protein cage nanoparticles are widely used as targeted delivery nanoplatforms, because they have well-defined symmetric architectures, high biocompatibility, and enough plasticity to be modified to produce a range of different functionalities. Targeting peptides and ligands are often incorporated on the surface of protein cage nanoparticles. In this research, we adopted the SpyTag/SpyCatcher protein ligation system to covalently display target-specific affibody molecules on the exterior surface of bacteriophage P22 virus-like particles (VLP) and evaluated their modularity and efficacy of targeted delivery.

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To characterize the immuno-stimulating ingredient from the Korean citrus, Cheongkyool, a crude polysaccharide (CCE-0) was isolated from the pectinase digests of Cheongkyool peels, from which the complex polysaccharide CCE-I was purified to homogeneity by gel filtration. CCE-I highly enhanced the production of IL-6, TNF-α, and NO in RAW 264.7 cell lines.

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To examine the anti-metastatic activities of polysaccharides in broccoli, purified polysaccharides (BCE-I, -II, and -III) were isolated by fractionation of broccoli enzyme extracts and subsequent ethanol precipitation. BCE-I mainly consisted of galactose and arabinose, whereas BCE-II mainly consisted of galacturonic acid and rhamnose, and BCE-III mainly consisted of rhamnose and galactose. Of the three fractions, stimulation of murine peritoneal macrophages by BCE-I showed the greatest enhancement of tumor necrosis factor-α, interleukin (IL)-12, and IL-6 secretion.

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Protein cage nanoparticles are made of biomaterials, proteins, and have well-defined cage-like architectures designed and built by nature. They are composed of multiple copies of one or a small number of chemically identical subunits having a highly uniform nano-size and symmetric structure. Protein cage nanoparticles have genetic and chemical plasticity amenable to simultaneously introducing multiple cell-specific targeting ligands, diagnostic agents, and their corresponding therapeutic agents at desired sites depending on its purpose.

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Article Synopsis
  • The fabrication of functional nanostructures is crucial in nanotechnology because they have unique properties compared to their individual components.* -
  • Protein cage nanoparticles, like genetically modified lumazine synthase, serve as effective templates to create dual-functional nanobuilding blocks by covalently attaching enzymes and protein ligands.* -
  • Using layer-by-layer assembly, these building blocks form 3D nanoreaction clusters that exhibit greater enzymatic activity than flat structures, offering new possibilities for developing biosensor devices based on protein nanoparticles.*
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