Atomic-scale materials are engaging in complex dialogues with our immune system's master regulators
Deep within your body, a sophisticated security system operates around the clock. Dendritic cells act as its elite intelligence agents—patrolling tissues, collecting foreign "signatures," and deciding when to activate the body's defenses. Today, scientists are investigating how an emerging class of two-dimensional nanomaterials, including graphene oxide, molybdenum disulfide, and boron nitride, influence these crucial cellular gatekeepers. What they're discovering could revolutionize how we approach everything from cancer therapy to vaccine development.
These atomic-scale sheets, some just one layer of atoms thick, possess extraordinary physical and chemical properties that have generated excitement across medicine. As they increasingly find applications in drug delivery, bioimaging, and tissue engineering, understanding their interaction with our immune system has become critically important. Recent research reveals a fascinating picture: these materials don't simply bypass our biological defenses—they engage in complex dialogues with dendritic cells that can either enhance or suppress immune responses, depending on their structure, size, and chemical properties.
Dendritic cells patrol tissues throughout the body, constantly sampling their environment for potential threats and foreign substances.
After encountering threats, dendritic cells migrate to lymph nodes where they "teach" T cells which invaders to attack through antigen presentation.
Dendritic cells (DCs) are often called the "sentinels" of the immune system. Residing in tissues throughout the body, they constantly sample their environment for potential threats. When they encounter foreign substances, they undergo a carefully orchestrated maturation process, migrating to lymph nodes where they present antigens to T cells, effectively "teaching" them which invaders to attack.
This antigen-presenting function makes DCs crucial coordinators of both innate immunity (our first line of defense) and adaptive immunity (the highly specific, memory-based response that vaccines seek to harness). Their ability to dictate the type, strength, and duration of immune reactions has placed them at the center of immunotherapy research, particularly for cancer treatment.
When dendritic cells encounter 2D nanomaterials, the interaction occurs at multiple levels. The materials may be internalized, interact with cell surface receptors, or trigger signaling pathways that ultimately influence DC maturation, cytokine production, and T cell activation capacity.
Nanomaterials are taken up by dendritic cells
Interaction with cell surface receptors
Triggering of intracellular signaling pathways
Altered maturation, cytokine production, and T cell activation
Among 2D materials, graphene oxide (GO) has received the most research attention regarding immune interactions. GO is an oxidized form of graphene containing various oxygen-containing functional groups that make it more readily dispersible in biological fluids than pristine graphene.
Research has revealed that small and large GO flakes differentially influence dendritic cell function. One study found that while small GO flakes enhanced antigen presentation to CD4+ T cells, large GO flakes augmented CD8+ T cell proliferation and their production of IFN-γ and granzyme B 3 .
The same 2020 study also performed whole-transcriptome sequencing analysis, finding that both mono-GO and multi-GO altered expression of immune-related genes including H2-DMb1, Fas, Cd244, and others involved in immune system processes 8 .
| GO Property | Experimental Finding | Immunological Impact |
|---|---|---|
| Flake Size | Small flakes enhance CD4+ T cell activation; large flakes enhance CD8+ T cell activation | Can steer adaptive immunity toward different responses |
| Layer Number | Multi-layer GO more toxic than mono-layer GO; mono-layer causes cell aggregation | Safety profile and cellular interactions depend on layer number |
| Surface Chemistry | PEG-functionalized GO suppresses CD83 expression at high concentrations | Can inhibit dendritic cell maturation |
| Concentration | Lower concentrations better tolerated than higher concentrations | Dose-dependent effects on viability and function |
MoS₂ has shown exceptional promise in cancer theranostics due to its unique optical properties and high surface area . Unlike early 2D materials like graphene, which can exhibit high toxicity, MoS₂ displays minimal toxicity and robust chemical stability . Its ultrahigh surface-to-volume ratio makes it a versatile nanoplatform for loading various therapeutic agents.
A 2023 study investigated effects of industrially produced 2D MoS₂ materials in primary human basophils, highlighting the importance of understanding immune interactions across different cell types 4 . Though basophils differ from dendritic cells, this research underscores the broader investigation into how 2D materials interact with immune cells.
Often called "white graphene," boron nitride is known for its excellent thermal stability and electrical insulation properties. In biomedical applications, research has primarily focused on its use in composite materials. A 2025 study investigated PMMA reinforced with nanographene oxide and boron nitride, finding that the combination enhanced hydrophilicity and antimicrobial properties 6 .
While this study didn't directly address dendritic cell interactions, it demonstrates BN's potential in biomaterial applications where immune compatibility is crucial.
| Material | Key Properties | Known Immune Effects |
|---|---|---|
| Graphene Oxide | Tunable conductivity, amphiphilic nature, various functional groups | Size-dependent T cell polarization, layer-dependent toxicity, concentration-dependent maturation suppression |
| Molybdenum Disulfide | Minimal toxicity, chemical stability, strong NIR absorption | Limited research on dendritic cells specifically; generally favorable biocompatibility |
| Boron Nitride | Thermal stability, electrical insulation, mechanical strength | Mostly studied in composites; antimicrobial effects observed when combined with nGO |
To understand how researchers investigate these nanomaterial-immune interactions, let's examine a key 2022 study published in the Bulletin of Experimental Biology and Medicine 7 . This experiment provides a clear example of the methodologies and findings in this field.
The researchers made several important observations:
The suppression of CD83 represents a potentially significant finding, as this surface marker plays a crucial role in dendritic cells' ability to effectively activate T cells. This suggests that at certain concentrations, GO might actually have immunosuppressive effects by interfering with dendritic cell maturation—a property that could be either beneficial or problematic depending on the clinical context.
| Parameter Measured | Finding | Significance |
|---|---|---|
| Cell viability | No significant effect | GO nanoparticles not overtly toxic to dendritic cells |
| Nanoparticle uptake | Concentration-dependent; higher concentration increased uptake | Dendritic cells actively internalize GO nanoparticles |
| CD83 expression | Suppressed by P-GO at 25 μg/ml | Suggests impaired dendritic cell maturation |
| Effect of PEG type | No significant difference between linear and branched PEG | Surface functionalization type less important than concentration |
The growing understanding of how 2D materials interact with dendritic cells opens exciting possibilities for precision immunotherapy. The ability of graphene oxide to differentially activate CD4+ versus CD8+ T cells based on flake size suggests these materials could be engineered to create tailored immune responses for specific clinical needs—such as enhancing cancer vaccines or suppressing autoimmune reactions.
However, significant challenges remain. Researchers must better understand the long-term fate of these materials in the body, their biodistribution, and potential accumulation effects. The concentration-dependent suppression of dendritic cell maturation by GO nanoparticles highlights the importance of careful dosing in therapeutic applications.
Future research will likely focus on surface engineering to enhance desired immune interactions while minimizing unintended effects, and developing composite materials that combine the advantages of multiple nanomaterials. As these technologies advance, the dialogue between 2D materials and our immune sentinels may yield powerful new approaches to medicine—harnessing atomic-scale materials to direct our body's most sophisticated defense systems.