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Related Concept Videos

Metal-Ligand Bonds02:51

Metal-Ligand Bonds

The hemoglobin in the blood, the chlorophyll in green plants, vitamin B-12, and the catalyst used in the manufacture of polyethylene all contain coordination compounds. Ions of the metals, especially the transition metals, are likely to form complexes.
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
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Valence Bond Theory

Coordination compounds and complexes exhibit different colors, geometries, and magnetic behavior, depending on the metal atom/ion and ligands from which they are composed. In an attempt to explain the bonding and structure of coordination complexes, Linus Pauling proposed the valence bond theory, or VBT, using the concepts of hybridization and the overlapping of the atomic orbitals. According to VBT, the central metal atom or ion (Lewis acid) hybridizes to provide empty orbitals of suitable...
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Stimuli-activated drug delivery systems are designed to release drugs in response to specific physical, chemical, or biological stimuli. These systems often utilize hydrogels—three-dimensional, hydrophilic polymer networks capable of swelling in aqueous environments and retaining significant fluid volumes. Upon exposure to particular stimuli, these hydrogels undergo structural transitions that allow the embedded drug to be released. Due to this adaptive behavior, such systems are also called...

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Lanthanide-Nucleotide Coordination Nanoparticles for STING Activation.

Zichao Luo1, Xiuqi Liang2, Tao He2

  • 1Department of Chemistry, National University of Singapore, Singapore 117543, Singapore.

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|August 29, 2022
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New lanthanide nanoparticles act as STING agonists, enhancing immune responses against viruses and cancer. This cost-effective platform offers potent delivery for improved immunotherapy and vaccine development.

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Area of Science:

  • Immunology
  • Nanotechnology
  • Biochemistry

Background:

  • Stimulator of interferon genes (STING) activation is crucial for antiviral and antitumor immunity.
  • Synthetic STING agonists like 2'3'-cGAMP show promise but face challenges in synthesis, dosage, and systemic response.
  • Developing accessible and effective STING agonist delivery systems is essential for immunotherapy.

Purpose of the Study:

  • To design and synthesize novel 2'3'-cGAMP surrogates using lanthanide-based nanoparticles.
  • To evaluate the efficacy of these nanoparticles in stimulating immune responses and as vaccine adjuvants.
  • To explore their potential for cancer immunotherapy and antiviral applications.

Main Methods:

  • Synthesis of 2'3'-cGAMP surrogate nanoparticles via reactions of AMP, GMP, and lanthanides.
  • In vitro assessment of type-I interferon (IFN) response in mouse macrophages and human monocytes.
  • In vivo evaluation of STING-targeted adjuvant effects on dendritic cell maturation, antigen presentation, antibody production, cytokine release, and tumor growth inhibition.

Main Results:

  • Lanthanide nanoparticles effectively stimulate type-I IFN response in immune cells.
  • Europium-based nanoparticles enhance dendritic cell maturation and MHC class I antigen presentation.
  • Nanovaccines significantly boost anti-OVA antibody and cytokine (IL-5, IFN-γ, IFN-α/β) production, inhibit tumor growth, and prolong survival compared to controls.

Conclusions:

  • Lanthanide-based nanoparticles provide a readily accessible and potent platform for STING agonist delivery.
  • This approach enables robust humoral and cellular immunity, offering a cost-effective strategy for cancer immunotherapy and vaccine development.
  • The supramolecular chemistry with lanthanides opens new avenues for efficient therapeutic delivery of STING agonists.