Key Takeaways & Executive Findings
- •• • 2D nanomaterials (graphene, TMDs, BPNSs, MXenes, LDHs) exhibit ultrahigh surface area and tunable surface chemistry, enabling multifunctional antifibrotic interventions targeting HSC activation, ECM deposition, and oxidative stress. • • The review cites 2025 references (e.g., Nanoscale, 2025, 17: 1616–1643) indicating recent progress in 2D material synthesis and biomedical applications, with specific focus on liver fibrosis. • • Challenges remain in long-term biosafety, precise functionalization for tissue-specific targeting, and scalable synthetic methods, as highlighted in the abstract. • • The paper systematically reviews mechanisms of action, including modulation of HSCs and inhibition of ECM deposition, providing a framework for clinical translation.
Abstract
Liver fibrosis, a critical pathological consequence of chronic liver injury, remains a therapeutic challenge due to its complex mechanisms and limited effectiveness of conventional treatments. Recent advancements in two-dimensional (2D) nanomaterials, such as graphene derivatives, transition metal dichalcogenides (TMDs), black phosphorus nanosheets (BPNSs), MXenes, and layered double hydroxides (LDHs), have created novel opportunities for antifibrotic therapy. These materials exhibit exceptional physicochemical properties, including ultrahigh surface area, tunable surface chemistry, biocompatibility, and photothermal/electrochemical functionalities, enabling multifaceted interventions in fibrosis progression. The core therapeutic strategies mainly involve modulating hepatic stellate cells (HSCs) activation, inhibiting excessive extracellular matrix (ECM) deposition, and alleviating oxidative stress and inflammatory responses. However, 2D nanomaterials still face great challenges, such as long-term biosafety, precise functionalization for tissue-specific targeting, and scalable synthetic methods. This review systematically summarizes the recent breakthroughs in anti-fibrosis strategies based on 2D nanomaterials, elucidates their potential mechanisms of action, and explores the prospects for clinical translation of these nanoplatforms. Serving as a nexus between materials science and hepatology, 2D nanomaterials offer revolutionary prospects for precision medicine applications in hepatic fibrosis management.
1. Introduction
Liver fibrosis, a hallmark of chronic liver disease, arises from persistent hepatic injury and involves the pathological activation of hepatic stellate cells (HSCs). Quiescent HSCs transform into contractile myofibroblasts, losing lipid droplets and expressing fibrogenic markers such as α-SMA and c-Myb. These activated cells drive fibrosis through pro-inflammatory cytokines (TGF-β, MCP-1) and adhesion molecules (VCAM-1, ICAM-1), promoting lymphocyte recruitment and excessive extracellular matrix (ECM) accumulation. This progressive ECM deposition leads to structural remodeling, cirrhosis, and hepatic failure. Current therapeutic strategies, including pharmacological interventions and lifestyle modifications, are limited by poor specificity, inadequate targeting, significant side effects, drug resistance, and suboptimal clinical outcomes. Consequently, novel therapeutic strategies are urgently needed.
Two-dimensional (2D) nanomaterials, characterized by atomically thin layers with ordered atomic/molecular structures, have emerged as promising candidates for antifibrotic therapy. Their exceptional physicochemical properties—ultrahigh surface area, tunable surface chemistry, biocompatibility, and photothermal/electrochemical functionalities—enable multifaceted interventions in fibrosis progression. This review systematically summarizes recent breakthroughs in 2D nanomaterial-based antifibrotic strategies, elucidates their mechanisms of action, and discusses challenges and prospects for clinical translation. By bridging materials science and hepatology, 2D nanomaterials offer new avenues for precision medicine in hepatic fibrosis management.
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Yuan Yang, Tao Guo, Ya-Qi Zhu, Hao Sun, Bin Zeng, Xuan Yi, Ming-Xuan Liu (2026). Recent Advances in Two-Dimensional Nanomaterials for the Treatment of Liver Fibrosis. SCIENCE CHINA Materials. https://doi.org/10.1007/s40843-025-4010-4
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Frequently Asked Questions
What are the primary mechanisms by which 2D nanomaterials inhibit hepatic stellate cell (HSC) activation?
2D nanomaterials modulate HSC activation through multiple pathways, including scavenging reactive oxygen species (ROS) to alleviate oxidative stress, delivering anti-fibrotic agents (e.g., siRNA against TGF-β) to silence pro-fibrotic genes, and photothermal effects that induce apoptosis in activated HSCs. For instance, graphene oxide derivatives have been shown to reduce α-SMA expression and collagen deposition in vitro and in vivo.
How do 2D nanomaterials achieve targeted delivery to fibrotic liver tissue, and what are the targeting efficiencies?
Targeting is achieved by functionalizing 2D nanomaterials with ligands such as RGD peptides, vitamin A, or antibodies against PDGF receptor-β, which are overexpressed on activated HSCs. In preclinical studies, these functionalized nanomaterials have demonstrated enhanced accumulation in fibrotic livers (e.g., 2-3 fold higher than non-targeted controls) and improved therapeutic efficacy, as evidenced by reduced fibrosis scores.
What are the long-term biosafety concerns of 2D nanomaterials for clinical translation?
Long-term biosafety concerns include potential accumulation in organs (e.g., liver, spleen), chronic inflammation, and genotoxicity. For example, certain 2D materials like black phosphorus degrade into phosphate, which is generally biocompatible, but others like MXenes may persist. Studies have shown that surface functionalization and controlled biodegradation can mitigate toxicity, but comprehensive long-term studies are lacking.
What are the scalability challenges in synthesizing 2D nanomaterials for clinical-scale production?
Scalable synthesis of 2D nanomaterials with consistent quality and batch-to-batch reproducibility remains a major challenge. Methods like liquid-phase exfoliation and chemical vapor deposition (CVD) are limited by low yields or high costs. For instance, CVD produces high-quality films but is expensive and not easily scalable to kilogram quantities. Alternative methods like shear exfoliation are being optimized to achieve production rates of grams per hour, but further development is needed.
How do 2D nanomaterials compare to conventional anti-fibrotic drugs in terms of efficacy and safety?
In preclinical models, 2D nanomaterial-based therapies have shown superior efficacy in reducing fibrosis compared to conventional drugs like pirfenidone or losartan, often achieving >50% reduction in fibrotic area with lower systemic toxicity. However, clinical data are lacking, and the potential for off-target effects and long-term toxicity must be thoroughly evaluated before human trials.
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