zinc ions

Overview

Zinc ions (Zn²⁺) are divalent cationic forms of the essential trace element zinc, and they play fundamental roles across a vast range of biological processes. As a critical micronutrient, Zn²⁺ serves as a structural cofactor for hundreds of enzymes and transcription factors, participating in DNA synthesis, protein folding, cellular signaling, and immune function. At the molecular level, zinc coordinates with nitrogen, oxygen, and sulfur donor atoms in proteins — particularly through histidine, cysteine, glutamate, and methionine residues — to stabilize tertiary structures and catalytic sites. This coordination chemistry underpins zinc's importance in processes ranging from gene expression regulation to antioxidant defense.

Beyond its homeostatic roles, Zn²⁺ has garnered significant biomedical attention for its capacity to modulate innate immune signaling, induce oxidative stress in aberrant cells, and interfere with tumor metabolism. In the context of cancer biology, elevated or dysregulated intracellular Zn²⁺ concentrations can disrupt mitochondrial function, activate immunogenic cell death (ICD) pathways, and trigger nucleic acid sensing cascades such as the cGAS-STING pathway. These properties have made Zn²⁺ a compelling active component in next-generation nanomedicine platforms, where controlled ion release within the tumor microenvironment (TME) is exploited to achieve synergistic therapeutic effects alongside conventional drugs and immunotherapy.

Recent Publications Focus

Below is a summary of the newest research publications targeting zinc ions (sorted by publication date).

Recent studies have explored zinc ions as versatile therapeutic components in smart delivery systems for infection control, cancer therapy, and crop protection. In biofilm-associated infection, a magnetically actuated microrobotic system used a pH-responsive ZIF-8 coating to provide immunomodulatory Zn2+ release alongside mechanical biofilm disruption, leading to effective biofilm removal, macrophage polarization toward the M2 phenotype, and enhanced tissue regeneration in a rat periprosthetic joint infection model. In a separate agricultural application, a dual pH-responsive double network hydrogel released Zn2+ together with zhongshengmycin and L-phenylalanine under acidic conditions, producing antibacterial activity, activating plant disease resistance pathways, and improving tomato wilt control in field settings.

Several publications focused on zinc ions in targeted nanocarriers for oncology. A hybrid nanogel system for sialic acid-overexpressing lung cancers used DNA-mediated chelation of doxorubicin or Zn2+ and pH-responsive release to improve tumor targeting and induce apoptosis, with in vivo suppression of H1299 xenograft growth. In malignant pleural effusion, DHA@ZIF-8 nanoparticles released zinc ions and dihydroartemisinin in lysosomes, where they acted as direct inhibitors of OCT4 and promoted M1 macrophage polarization while dampening M2 polarization through the OCT4/NF-κB/M-CSF axis. Another study developed an enzyme-activatable nanosystem for breast cancer bone metastasis in which acidic microenvironment-triggered Zn2+ release was combined with MMP-2-activated imaging and photothermal therapy, resulting in apoptosis, reduced migration and invasion, and strong suppression of metastatic tumor growth without observable systemic toxicity.

Other work highlighted zinc ions as modulators of tumor metabolism and antitumor immunity. In hepatocellular carcinoma, pH-responsive gelatin microspheres encapsulating zinc sulfide nanoparticles delivered Zn2+ and hydrogen sulfide to suppress the HIF-1α/VEGF axis and glycolytic metabolism, promote vascular normalization, induce immunogenic cell death, and enhance anti-PD-1 therapy. In advanced prostate cancer, a ROS-responsive PTX-Zn nanoparticle co-delivered paclitaxel and Zn2+, where Zn2+ enhanced cGAS-STING signaling by promoting cGAS-DNA binding and inducing mitochondrial damage, reprogramming the tumor microenvironment toward a more immunogenic state and improving the effect of anti-PD-L1 therapy.

Beyond delivery platforms, one study examined the molecular chemistry of zinc-ion binding itself. Methionine-driven covalent chelation by linusorb peptides showed that Zn2+ binds specifically to methionine residues, with unoxidized peptides exhibiting stronger binding than oxidized forms. This interaction stabilized peptide structure and inhibited Zn2+-catalyzed lipid oxidation, underscoring the importance of sulfur-containing residues in zinc coordination and redox-sensitive binding behavior.

Background PMIDs

• [PMID 41949057]
• [PMID 41981450]

Method PMIDs

• [PMID 41935010]
• [PMID 41962772]
• [PMID 42302127]

Target PMIDs

• [PMID 41628534]
• [PMID 41863922]
• [PMID 41985455]
• [PMID 41999640]
• [PMID 42020944]
• [PMID 42276469]
• [PMID 42285939]
• [PMID 42406953]