Dataset Information

Antibody-Conjugated Magnetic Nanoparticle Therapy for Inhibiting T-Cell Mediated Inflammation.

ABSTRACT: Tolerance induction is critical for mitigating T cell-mediated inflammation. Treatments based on anti-CD3 monoclonal antibody (mAb) play a pivotal role in inducing such tolerance. Anti-CD3 mAb conjugated with dextran-coated magnetic nanoparticles (MNPs) may induce inflammatory tolerance is posited. MNPs conjugated with anti-CD3 mAb (Ab-MNPs) are characterized using transmission and scanning electron microscopy, and their distribution is assessed using a nanoparticle tracking analyzer. Compared to MNPs, 90% of Ab-MNPs increased in size from 54.7 ± 0.5 to 71.7 ± 2.7 nm. The in vitro and in vivo studies confirmed the therapeutic material as nontoxic and biocompatible. Mice are administered various dosages of Ab-MNPs before receiving concanavalin-A (ConA), an inflammation inducer. Preadministration of Ab-MNPs, as opposed to MNPs or anti-CD3 mAb alone, significantly reduced the serum levels of interferon-γ and interleukin-6 in ConA-treated mice. Additionally, the transdermal stamp patch as an effective delivery system for Ab-MNPs is validated. This study demonstrates the utility of the Ab-MNP complex in pathologies associated with T cell-mediated hyperinflammation, such as organ transplantation and COVID-19.

SUBMITTER: Hasan M

PROVIDER: S-EPMC10953552 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Antibody-Conjugated Magnetic Nanoparticle Therapy for Inhibiting T-Cell Mediated Inflammation.

Hasan Mahbub M Choi Jong-Gu JG Akter Hafeza H Kang Hasung H Ahn Meejung M Lee Sang-Suk SS

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20231231 11

Tolerance induction is critical for mitigating T cell-mediated inflammation. Treatments based on anti-CD3 monoclonal antibody (mAb) play a pivotal role in inducing such tolerance. Anti-CD3 mAb conjugated with dextran-coated magnetic nanoparticles (MNPs) may induce inflammatory tolerance is posited. MNPs conjugated with anti-CD3 mAb (Ab-MNPs) are characterized using transmission and scanning electron microscopy, and their distribution is assessed using a nanoparticle tracking analyzer. Compared t ...[more]

PMID: 38161230

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Project description:Metal-based chemotherapeutics like cisplatin are widely employed in cancer treatment. In the last years, the design of redox-active (transition) metal complexes, such as of copper (Cu), has attracted high interest as alternatives to overcome platinum-induced side-effects. However, several challenges are still faced, including optimal aqueous solubility and efficient intracellular delivery, and strategies like the use of cell-penetrating peptides have been encouraging. In this context, we previously designed a Cu(II) scaffold that exhibited significant reactive oxygen species (ROS)-mediated cytotoxicity. Herein, we build upon the promising Cu(II) redox-active metallic core and aim to potentiate its anticancer activity by rationally tailoring it with solubility- and uptake-enhancing functionalizations that do not alter the ROS-generating Cu(II) center. To this end, sulfonate, arginine and arginine-rich cell-penetrating peptide (CPP) derivatives have been prepared and characterized, and all the resulting complexes preserved the parent Cu(II) coordination core, thereby maintaining its reported redox capabilities. Comparative in vitro assays in several cancer cell lines reveal that while specific solubility-targeting derivatizations (i.e., sulfonate or arginine) did not translate into an improved cytotoxicity, increased intracellular copper delivery via CPP-conjugation promoted an enhanced anticancer activity, already detectable at short treatment times. Additionally, immunofluorescence assays show that the Cu(II) peptide-conjugate distributed throughout the cytosol without lysosomal colocalization, suggesting potential avoidance of endosomal entrapment. Overall, the systematic exploration of the tailored modifications enables us to provide further understanding on structure-activity relationships of redox-active metal-based (Cu(II)) cytotoxic complexes, which contributes to rationalize and improve the design of more efficient redox-mediated metal-based anticancer therapy.

Dataset Information

Antibody-Conjugated Magnetic Nanoparticle Therapy for Inhibiting T-Cell Mediated Inflammation.

Publications

Antibody-Conjugated Magnetic Nanoparticle Therapy for Inhibiting T-Cell Mediated Inflammation.

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