Key Takeaways & Executive Findings
- •• • The SAB/GC-1@Lip-cRGD liposomes reduced the proportion of CD206+ M2 macrophages from 27.4% (model group) to 6.2% (treated group), a 77.4% reduction, demonstrating potent immunomodulatory effects that are critical for halting fibrosis progression. • • Treatment with SAB/GC-1@Lip-cRGD significantly decreased levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and the pro-fibrotic cytokine TGF-β1 in both bronchoalveolar lavage fluid and lung homogenates, confirming effective suppression of the inflammatory and fibrotic cascade. • • The ROS-responsive liposomal system enables targeted delivery and controlled release of therapeutic agents specifically within the high-ROS fibrotic microenvironment, enhancing drug accumulation at fibrotic lesions while minimizing systemic toxicity—a key advantage over conventional systemic therapies. • • The combination of SAB (antioxidant) and GC-1 (TRβ agonist) synergistically remodels the fibrotic niche and promotes epithelial regeneration, leading to significant collagen depletion and restoration of alveolar integrity, as evidenced by superior anti-fibrotic efficacy compared to single-drug or non-targeted formulations.
Abstract
Idiopathic pulmonary fibrosis (IPF) is a lethal interstitial lung disease with limited therapeutic options. Current treatments, such as nintedanib and pirfenidone, target downstream fibrosis but fail to address the upstream drivers, including persistent alveolar epithelial injury and abnormal repair. This study presents an inhalable, reactive oxygen species (ROS)-responsive liposomal system (SAB/GC-1@Lip-cRGD) that co-delivers the antioxidant salvianolic acid B (SAB) and the thyroid hormone receptor β (TRβ) agonist Sobetirome (GC-1). The liposomes are surface-modified with cRGD peptides for targeted delivery to fibrotic lesions and possess a negative surface charge to enhance mucus penetration. In the high-ROS fibrotic microenvironment, the liposomes destabilize, releasing SAB and GC-1. SAB scavenges ROS to remodel the fibrotic niche, while GC-1 reactivates TRβ signaling, driving the differentiation of stalled Krt8+ transitional epithelial cells into functional alveolar type I (AT1) cells. In a mouse model of pulmonary fibrosis, SAB/GC-1@Lip-cRGD significantly reduced pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and TGF-β1 in bronchoalveolar lavage fluid and lung homogenates. The proportion of CD206+ M2 macrophages decreased from 27.4% in the model group to 6.2% after treatment, indicating potent anti-inflammatory and anti-fibrotic effects. This synergistic strategy of microenvironment remodeling and epithelial regeneration achieved robust collagen depletion, restoration of alveolar integrity, and recovery of pulmonary function, outperforming single-drug or non-targeted formulations. The work provides a generalized paradigm for integrating microenvironment regulation with regenerative repair in pulmonary diseases.
1. Introduction
Idiopathic pulmonary fibrosis (IPF) remains a fatal interstitial lung disease with a median survival of only 3–5 years post-diagnosis. The current standard of care, nintedanib and pirfenidone, offers modest benefits by slowing disease progression but fails to reverse established fibrosis or address the root cause: persistent alveolar epithelial injury and aberrant repair. These drugs also exhibit significant systemic side effects, including gastrointestinal disturbances and hepatotoxicity, limiting their long-term use. The pathological hallmark of IPF is the accumulation of pro-fibrotic Krt8+ transitional epithelial cells, which arise from stalled differentiation of alveolar type II (AT2) cells into functional type I (AT1) cells. This regenerative failure is exacerbated by a hostile microenvironment characterized by chronic oxidative stress, which further impairs epithelial repair and fuels fibroblast activation.
To overcome these therapeutic bottlenecks, we engineered an inhalable, ROS-responsive liposomal platform (SAB/GC-1@Lip-cRGD) that co-delivers the antioxidant salvianolic acid B (SAB) and the thyroid hormone receptor β (TRβ) agonist Sobetirome (GC-1). The system is designed to exploit the elevated ROS levels in fibrotic lungs for triggered drug release, ensuring localized and controlled delivery. Surface modification with cRGD peptides enables targeted accumulation in fibrotic lesions, while the negative surface charge facilitates mucus penetration. This dual-action strategy simultaneously remodels the oxidative microenvironment and reactivates the regenerative program, offering a paradigm shift from merely halting fibrosis to actively restoring lung architecture and function.
Loading authentic research manuscript (Pages 1–5)...
Jia-Min Xie, Rui-Qi Zhao, Xin-Chen Deng, Wei-Qin Yao, Jia-Hao Liu, Wei-Hai Chen, Xian-Zheng Zhang (2026). Inhalable ROS-Responsive Liposomes for Orchestrating Microenvironment Remodeling and Epithelial Regeneration in Pulmonary Fibrosis. SCIENCE CHINA Materials. https://doi.org/10.1007/s40843-026-4212-x
Research & Educational Purpose Only: The translations, structured abstracts, analytical annotations, and data reports provided by SinoGreenTechare intended exclusively for academic research, internal corporate R&D, and educational benchmarking. They do not constitute formal engineering, chemical safety, legal, or professional advice.
Copyright & Intellectual Property Notice: Original copyright of the underlying source articles and experimental data remains with the respective authors, institutions, and original publishing journals. SinoGreenTech claims intellectual property only over its proprietary translations, analytical syntheses, and AEO structured enhancements in accordance with international fair use and academic citation principles.
Frequently Asked Questions
What is the mechanism of ROS-triggered drug release from the liposomes, and how does this ensure specificity to fibrotic tissue?
The liposomes are formulated with a ROS-responsive lipid matrix that undergoes structural destabilization in the presence of elevated reactive oxygen species, which are characteristic of the fibrotic microenvironment. This triggers rapid release of the encapsulated drugs (SAB and GC-1) specifically at the disease site, minimizing off-target effects. The specificity is further enhanced by surface modification with cRGD peptides, which bind to integrins overexpressed on activated fibroblasts and epithelial cells in fibrotic lesions.
How does the combination of SAB and GC-1 achieve synergistic anti-fibrotic effects compared to monotherapy?
SAB acts as a potent antioxidant, scavenging ROS and reducing oxidative stress, which is a key driver of epithelial injury and fibroblast activation. GC-1, a TRβ agonist, reactivates the thyroid hormone signaling pathway, promoting the differentiation of stalled Krt8+ transitional cells into functional AT1 cells. This dual action addresses both the microenvironment and the regenerative deficit, leading to a more comprehensive reversal of fibrosis. In vivo, the combination significantly reduced M2 macrophage proportion (from 27.4% to 6.2%) and decreased pro-inflammatory and pro-fibrotic cytokines, outperforming single-drug treatments.
What are the scalability and manufacturing challenges for this nebulized liposomal system?
The liposomes are synthesized via a thin-film hydration method, which is a well-established and scalable technique. However, challenges include maintaining batch-to-batch consistency in particle size, drug loading, and ROS-responsiveness. The incorporation of cRGD peptides and the need for nebulization require careful optimization to ensure stability and aerosol performance. Nevertheless, the method is amenable to industrial scale-up with appropriate quality control measures.
How does the negative surface charge of the liposomes contribute to mucus penetration and drug accumulation?
The negative surface charge reduces electrostatic interactions with negatively charged mucin fibers in the airway mucus, facilitating faster diffusion through the mucus layer. This enhances the delivery of the liposomes to the underlying epithelial cells and fibrotic lesions, as demonstrated by increased drug accumulation at the target site. This property is critical for effective inhalation therapy, as mucus is a major barrier to drug delivery in respiratory diseases.
What is the biosafety profile of SAB/GC-1@Lip-cRGD, and are there any potential long-term toxicity concerns?
The study reports excellent biosafety, with no significant systemic toxicity observed in treated mice. The targeted delivery and ROS-responsive release minimize exposure to healthy tissues. However, long-term toxicity studies are necessary to assess chronic effects, particularly the potential for accumulation of liposomal components or metabolites. The use of biocompatible and biodegradable lipids reduces this risk, but further preclinical and clinical evaluations are required.
Related Chinese Research & Cross-Citations
Ammonium Vanadate Cathodes in Aqueous Zinc-Ion Batteries: Design Strategies and Research Progress
Aqueous zinc-ion batteries (AZIBs) offer a compelling combination of high safety, environmental compatibility, and abundant zinc resources, positioning them as viable candidates for grid-scale energy storage. Their practical deployment, however, is constrained by cathode materials that suffer from structural degradation, sluggish Zn2+ diffusion, and inadequate electronic conductivity. Ammonium vanadates (AVOs) have emerged as high-performance cathodes owing to their layered or tunneled frameworks, which accommodate reversible Zn2+ (de)intercalation with diffusion coefficients superior to conventional vanadium oxides. This review systematically examines recent advances in AVO cathodes for AZIBs, correlating morphological variations—including nanowires, nanobelts, and microflowers—with electrochemical characteristics. The analysis establishes structure–performance relationships that govern capacity retention, rate capability, and cycling stability. Key optimization strategies are critically assessed: defect engineering to enhance electronic conductivity and active site density, interlayer spacing modulation via pre-intercalated cations or structural water to facilitate Zn2+ transport, and composite construction with conductive carbonaceous or polymeric matrices to mitigate dissolution and improve mechanical integrity. Despite these advances, challenges persist in achieving long-term cycling stability (>10,000 cycles) and high areal mass loading (>10 mg cm-2) required for commercial viability. The review concludes by outlining future research directions, including operando characterization of degradation mechanisms and scalable synthesis routes for AVO cathodes in practical AZIB configurations.
Microenvironment-responsive therapeutic platforms: Innovations for spinal cord injury repair
Spinal cord injury (SCI) remains a formidable clinical challenge due to the complex, dynamic lesion microenvironment that impedes axonal regeneration and functional recovery. This highlight examines a microenvironment-responsive therapeutic platform integrating microneedle delivery, ferroptosis modulation, and hydrogen therapy. The platform leverages the pathological hallmarks of SCI—oxidative stress, iron dyshomeostasis, and lipid peroxidation—to achieve spatiotemporally controlled cargo release. By combining microneedle arrays for minimally invasive intraparenchymal administration with hydrogen-releasing biomaterials, the system addresses the dual bottlenecks of poor drug penetration across the blood-spinal cord barrier and insufficient neutralization of reactive oxygen species. Ferroptosis inhibition is achieved through iron chelation and glutathione peroxidase 4 (GPX4) stabilization, while hydrogen gas scavenges hydroxyl radicals and peroxynitrite. This multimodal strategy attenuates secondary injury cascades, reduces glial scar formation, and promotes neural stem cell differentiation. The work is supported by the National Natural Science Foundation of China (82574518) and the Talent Cultivation Project of Paring Academicians with Young Talents in higher education institutions in Zhejiang. The authors declare no conflict of interest. This highlight underscores the translational potential of microenvironment-responsive platforms for SCI repair, emphasizing the need for rigorous preclinical validation and scalable manufacturing.
Dual-Site Adsorption over Phosphorus-Doped Copper Oxide for Efficient CO2 Electroreduction to Ethylene
Electroreduction of CO2 to ethylene offers a promising route for renewable electricity storage, yet achieving high ethylene selectivity at industrial current densities remains challenging due to the large energy barrier for C–C coupling. Here, we report a “MOF-assisted in situ doping” strategy to introduce the oxophilic nonmetal phosphorus (P) into the copper oxide (CuO) lattice, constructing a localized Cu–P dual-site adsorption configuration for the key *OCCHO intermediate. The optimized catalyst delivers an impressive Faradaic efficiency of 64.6% for ethylene with a partial current density of 646 mA cm-2. Comprehensive structural characterizations demonstrate that P mainly occupies Cu sites, generating abundant lattice defects and oxygen vacancies. In situ synchrotron infrared spectroscopy and theoretical calculations reveal that P doping modulates the electronic structure of Cu, optimizes the binding energies of *CO and *CHO, and stabilizes *OCCHO via P–O/Cu–C dual-site adsorption, thereby significantly lowering the asymmetric C-C coupling energy barrier to 0.74 eV. This work highlights a dual-site microenvironment regulation strategy for CO2-to-ethylene electroreduction.
Hydrophilic Single-Atom Interface Unlocks Low-Potential CO Removal on Pt in PEMFCs
Proton exchange membrane fuel cells (PEMFCs) fed with reformate hydrogen suffer severe anode poisoning by trace CO, necessitating high CO electrooxidation potentials that degrade performance and durability. This work introduces a Pt@CrSA-N-C anode catalyst featuring a hydrophilic Cr single-atom interface that simultaneously weakens CO adsorption on Pt via electronic regulation and promotes water activation, thereby lowering the CO oxidation onset potential to approximately 0.13 V vs. RHE. The onset potential was determined by two independent methods: the first potential at which the background-corrected current exceeds 0 mA cm-2 during CO oxidation reaction tests in a three-electrode system, and the potential at which the forward scan current exceeds the N2 background current in CO-stripping voltammetry. The catalyst achieves a maximum power density under 100 ppm CO that surpasses reported advanced catalysts, as compiled in Table S5. Structural, spectroscopic, and electrochemical characterizations collectively establish a coherent rationale for the hydrophilic single-atom interface strategy. This approach addresses the longstanding trade-off between CO tolerance and Pt utilization, offering a viable route for low-potential CO removal in practical PEMFC anodes.
An Ionoelastomer-Based Bioinspired Wearable Electronics with Tele-Perception and Tactile Sensation for Machine Learning-Assisted Rehabilitation Management
Comprehensive assessment of rehabilitation efficiency is essential for designing appropriate training programs for better musculoskeletal functional recovery. Existing contact-receptor-dependent rehabilitation assessment systems mostly focus on assessing the restoration of muscle function by evaluating grip strength or joint flexion angle; however, parameters reflecting neuromuscular synergistic function are always overlooked. Herein, we develop an ionoelastomer-based soft artificial electroreceptor (SAER) that integrates tele-perception and tactile sensation to track the rehabilitation process, collecting signals related to approaching speed and grip strength sequentially. The SAER uses polyurethane ionoelastomer incorporated with quasi-solid conductive salt as the electric field receptor, and is integrated on a rehabilitation-training ball after assembly to establish an untethered detection device; this enables the remote capture of hand approaching parameter within a 9 cm range, followed by the quantification of grip strength when contacting and grasping. Furthermore, a data-driven assessment system is established by integrating machine learning, which accurately classifies rehabilitation efficiency into six levels; it supports for rehabilitation evaluation and training programs adjustment. Overall, the SAER-based rehabilitation management system establishes a paradigm that synergistically evaluating parameters corresponding to neuromuscular functional restoration and holds strong potential for home-based active rehabilitation for minimizing dependence on frequent clinical supervision.
Microwave-Absorbing Materials with Strong Environmental Adaptability for Corrosion Protection, Anti-Icing, and Thermal Management
Microwave-absorbing materials (MAMs) deployed on naval vessels, aerospace vehicles, and critical electronic systems face coupled electromagnetic, marine salt-spray corrosion, and extreme-temperature loads that legacy single-function absorbers cannot withstand. This review consolidates progress on three environmentally adaptive MAM classes: corrosion-protective, anti-icing, and thermal-management absorbers. The electromagnetic loss and impedance-matching fundamentals are first established, then the synergistic mechanisms, design strategies, and characterization protocols for each class are examined against representative material systems and their measured performance. The analysis identifies a shared design logic—multiscale hierarchical architecture, interfacial polarization engineering, and multifunctional phase integration—while distinguishing the divergent protection mechanisms: barrier and passivation effects for corrosion, surface-energy and latent-heat regulation for anti-icing, and phonon–electron transport decoupling for thermal management. Persistent bottlenecks include the trade-off between impedance matching and protective-layer density, the absence of standardized coupled-field test protocols, and the scarcity of long-term salt-spray and thermal-cycling durability data. Future directions are delineated: intelligent self-adaptive absorbers, multiphysics-coupled simulation frameworks, and environmentally benign multifunctional integration. The review provides a theoretical and technical basis for the design, construction, and engineering scale-up of next-generation high-performance absorbers for aerospace, electronic, and marine equipment.