Science Advances
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2025
·Vol. 11
·期 11
·
IF 12.5
Zhuoyao Wu,Weiwei Zeng,Weitao Yang,Jinyan Yi,Dinghua Liu,Yan Xu,Chang Liu,Kexin Bian,Hui Wang,Bingbo Zhang
Liver fibrosis is an inevitable stage in the progression of most chronic liver diseases. Early diagnosis and treatment of liver fibrosis are crucial for effectively managing chronic liver conditions. However, there lacks a noninvasive and sensitive imaging method capable of early assessing fibrosis activity. Here, we report a molecular magnetic resonance imaging (MRI) probe for imaging fibroblast activation protein (FAP), which is overexpressed on activated hepatic stellate cells (HSCs) even in very early fibrotic livers. This method relies on FAP-catalyzed in situ self-assembly of its substrate probe that leads to the increase of the rotational correlation time (τR) of probe, thereby notably amplifies T1 MRI signal. Thanks to the superior specificity and efficiency of enzymatic reaction, our method has been validated as highly selective and sensitive to FAP in two liver fibrosis mouse models. By establishing a direct correlation between MRI signals and fibrosis activity, our method enables continuous monitoring of liver fibrotic disease progression and assessment of treatment responses.
研究领域:
医学影像学
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肝脏病学
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Chenglong Li,Shuhao Xu,Xin Li,Huaiyu Su,Can Qian,Yingying Hou,Sanjun Shi
Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by joint inflammation, damage, and disability. Activated fibroblast-like synoviocytes (FLSs), abundant in RA synovium, crucially facilitate disease progression. These activated FLSs drive RA pathogenesis by upregulating adhesion molecules, proinflammatory cytokines, chemokines, and major histocompatibility complex class II (MHC-II). This upregulation facilitates their interaction with CD4 + T cells, triggering an inflammatory cascade that exacerbates synovial inflammation. To address this, a DSPE-mPEG 2000 -GPA-KLVFF-decorated liposome loaded with dexamethasone (DPGK@Lipo-Dex) is developed to precisely target FLSs in arthritic joints. DPGK@Lipo-Dex achieves efficient binding to FLSs through a specific enzymatic interaction between fibroblast activation protein-α (FAP-α) and GPA, along with prolonged retention in the joints due to the fibrillar transformation of KLVFF. In vitro studies demonstrate that DPGK@Lipo-Dex enhances cellular uptake and reduces MHC-II expression on aggressive FLSs. In adjuvant-induced arthritis (AIA) rats, DPGK@Lipo shows specific distribution patterns that target both inflamed joints and FLSs. Treatment with DPGK@Lipo-Dex leads to a downregulation of MHC-II expression, a decrease in the number of activated T cells within the synovium, and a reduction in levels of proinflammatory mediators. Overall, DPGK@Lipo-Dex effectively suppresses FLSs-related responses and ultimately results in inflammatory remission. This makes DPGK@Lipo-Dex a promising candidate for nano-therapeutic treatment in rheumatoid arthritis.
研究领域:
免疫学
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纳米医学
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风湿病学
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分子靶向治疗
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药剂学
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转化医学
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DOI
PubMed
高影响因子
Polymer Chemistry
·
2013
·Vol. 4
·期 15
·4120-4125
·
IF 5.231
Xiaoyong Zhang,Junfeng Hui,Bin Yang,Yong Yang,Daidi Fan,Meiying Liu,Lei Tao,Yen Wei
PEGylation is a popular approach for the surface functionalization of nanoparticles to achieve improved properties and better performance. Herein, we developed a facile method for surface PEGylation of hydrophobic fluoridated hydroxyapatite (FAp):Ln3+ (Ln = Eu or Tb) nanorods via hydrophobic interactions between oleic acid and amphiphilic synthetic copolymers, which were synthesized through reversible addition-fragmentation chain transfer (RAFT) polymerization using stearyl methacrylate (SMA) and poly(ethylene glycol) methacrylate (PEGMA) as monomers. Our results demonstrated that the morphology and fluorescent properties of the FAp nanorods are not significantly changed by the PEGylation procedure, and the resulting FAp nanorods were found to be stable in aqueous solution. More importantly, these PEGylated FAp nanorods are biocompatible with cells and could be utilized for cell imaging applications. Therefore, we believe that the method described in this work is a simple, efficient and general strategy for the surface PEGylation of hydrophobic nanoparticles.
研究领域:
材料科学
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生物医学工程
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DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Haiyan Hong,Zhihao Zha,Ruiyue Zhao,Yang Luo,Wenbin Jin,Linlin Li,Ran Wang,Li Yan,Hui Wang,Karl Ploessl,Jinping Qiao,Lin Zhu,Hank F. Kung
Fibroblast activation protein (FAP) is selectively expressed in tumors and highly important for maintaining the microenvironment in malignant tumors. Radioisotope-labeled FAP inhibitors (FAPIs) were proven to be useful for diagnosis and radionuclide therapy of cancer and are under active clinical investigations. Ga-HBED complex displays a higher in vivo stability constant (log KGaL: 38.5), compared to that of Ga-DOTA (log KGaL: 21.3). Such advantage in stability constant suggests that it may be useful for development of alternative FAPI imaging agents. In this study, previously reported [68Ga]Ga-DOTA-FAPI-02 and -04 were converted to the corresponding [68Ga]Ga-HBED-CC-FAPI-02 and -04 derivatives ([68Ga]Ga-4, [68Ga]Ga-5, [68Ga]Ga-6, and [68Ga]Ga-7). It was found that substituting the DOTA chelating group with HBED-CC led to several unique and desirable tumor-targeting properties: (1) robust, fast, and high yield labeling─readily adaptable to a kit formulation; (2) high stabilities in vitro; (3) excellent FAP binding affinities (IC50 ranging between 4 and 7 nM) and improved cell uptake and retention (in HT1080 (FAP+) cells); and (4) excellent selective in vivo tumor uptake in nude mice bearing U87MG tumor. It appeared that Ga(III) chelation with HBED-CC improved the in vivo kinetics favoring higher tumor uptake and retention compared to the corresponding Ga-DOTA complex. Out of the four tested ligands the new [68Ga]Ga-HBED-CC-FAPI dimer, [68Ga]Ga-6, displayed the best tumor localization properties, and further studies are warranted to demonstrate that it is an alternative FAP imaging agent for cancer patients.
研究领域:
医学影像学
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肿瘤学
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DOI
PubMed
高影响因子
Bioactive Materials
·
2026
·
IF 23.6
Yongliang Jiang,Hao Li,Lin Yang,Shiwei Niu,Qi Zheng,Ping Yang,Limei Li,Gaosheng Yin,Shuangxiu Li,Hongdong Shi,Lin Sun,Di Lu
Ischemic heart disease, particularly myocardial infarction (MI), is a leading cause of global mortality, and the resulting myocardial fibrosis significantly impairs cardiac function, contributing to heart failure. Despite considerable efforts, effective therapeutic interventions for reversing myocardial fibrosis and restoring heart function remain elusive. Recent studies highlight the crucial role of metabolic reprogramming in the activation of cardiac fibroblasts (CFs) and their transformation into myofibroblasts, which drive fibrosis. Gastrodin (GAS), a phenolic glycoside derived from Gastrodia elata , has demonstrated promising anti-fibrotic and metabolic regulatory effects; however, its clinical application has been limited by poor pharmacokinetic properties and lack of targeted delivery. Here, we designed an intrapericardial (iPC) injection nanocomposite hydrogel incorporating FAP-targeted CAR-T cell membrane-coated GAS nanoparticles (FAP-CAR T CM@PPA-G NPs) within a pH/ROS-responsive CP/PCPD hydrogel. This innovative system achieves specific targeting of FAP-positive myofibroblasts, on-demand release of GAS triggered by pathological ROS and pH changes, and effective inhibition of fibrosis by modulating the KLF2/CREB5/HIF-1α/PFKFB3 metabolic axis. Our findings not only provide a novel therapeutic platform for post-MI fibrosis treatment but also elucidate the mechanistic basis of GAS's anti-fibrotic effects. This strategy offers significant promise for advancing the clinical translation of GAS-based therapies for myocardial fibrosis and heart failure.
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高影响因子
CELLULOSE
·
2023
·Vol. 30
·期 10
·6667-6677
·
IF 5.7
Zhang Yao,Hao Longyun
In this paper, a modified sericin containing active acryloyl groups (MSAA) was prepared by amidation reaction using acryloyl chloride and sericin as raw materials, and its structure was analyzed by FT-IR, fluorescence spectrum, zeta potential and 1 H NMR. The results showed that the active acrylyl groups were successfully introduced into the molecular chains of sericin. Then, MSAA and an alkaline crosslinking agent 1,3,5-triacroylaminohexahydro-s-triazine (FAP) were combined to finish cotton fabric in alkaline condition. Under alkaline condition, the anti-wrinkle effect of cotton fabric could be improved by finishing with MSAA and FAP. By measuring the wrinkle recovery angle, it was found that with the increase of MSAA content, the anti-wrinkle effect of cotton fabric was obviousy improved, without significant impact on the strength and whiteness of the fabric. In addition, the dyeing property and ultraviolet resistance of the finished fabric could be apparently improved.
研究领域:
纺织科学
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材料化学
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DOI
高影响因子
Journal of the American Chemical Society
·
2026
·
IF 16.6
Chenlong Wei,Xinzhu Shan,Yuxuan Huang,Bin Ma,Zhiqiang Zhao,Yian Fang,Chengrui Bai,Zihan Zhang,Peng Zhao,Huijuan Zhang,Yu Hou,Tianjiao Ji,Zhongtang Li,Song Song,Fei Xie,Lei Miao
The inefficient delivery of lipid nanoparticles (LNPs)-encapsulated mRNA to activated fibroblasts in fibrotic tissues remains a major challenge for antifibrotic therapy. To overcome this, we develop a fibrosis organ and cell unified-targeting system (FOCUS) for mRNA delivery with LNPs. FOCUS LNPs combines an ionizable lipid library (synthesized via Ugi multicomponent reactions) with fibroblast activation protein-α (FAP)-targeting lipid-like ligands. These LNPs achieve ∼3-fold and ∼12-fold greater mRNA expression in fibrotic liver and lung, along with ∼2–5-fold higher fibroblast distribution─unattainable by organ- or ligand-only targeting. As proof of concept, Pentraxin-2 mRNA (mPTX-2)-loaded FOCUS LNPs drive localized PTX-2 production in murine models of pulmonary and hepatic fibrosis, reducing collagen deposition by 60–80% while avoiding systemic side effects like impaired wound healing. Mechanistically, mPTX-2 FOCUS LNPs suppress monocyte-to-fibrocyte differentiation, M2 macrophage polarization, and fibroblast activation. This work establishes a precision mRNA delivery platform for fibrotic diseases, offering a safer and more effective therapeutic strategy.
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DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Xiaonan Wei,Chaoquan Lai,Xiaoyang Zhu,Aiyan Ji,Yeshan Qin,Shu Gao,Qiuyu Liu,Yonghao Li,Xuanyan Zhao,Hongyue Lou,Chunrong Qu,Zhen Cheng
Fibroblast activation protein (FAP) is an important target for the integrated diagnosis and treatment of tumors. However, FAP-targeted small molecule-based radiopharmaceuticals often face challenges such as low tumor uptake and short tumor retention, which hinder their biomedical and clinical applications. In this study, two radiolabeled FAP-targeted nanoprobes based on melanin nanoparticles (MNPs) were designed and developed in order to evaluate their potential for FAP-targeted theranostics. The excellent metal ion complexing property of melanin allowed 89Zr to be efficiently labeled on the MNP platform. After PEGylated MNPs were modified with small molecules FAPI-04 and GPFAPI-04 and radiolabeled with 89Zr to obtain [89Zr]Zr–F-MNPs and [89Zr]Zr-GPF-MNPs, these two nanoprobes achieved active targeting through FAPI ligands. The radiochemical purity of 89Zr-labeled nanoprobes remained above 90% in fetal bovine serum (FBS) solution in 72 h. In vitro experiments showed that both [89Zr]Zr–F-MNPs and [89Zr]Zr-GPF-MNPs were taken up by FAP high-expressing U87MG cells (2.58 ± 0.07% vs 3.00 ± 0.10% for 2 h; 2.93 ± 0.08% vs 3.62 ± 0.04% for 4 h). For the in vivo study, at 48 h postinjection (p.i.) of the nanoprobe, the U87MG tumor uptake of [89Zr]Zr–F-MNPs and [89Zr]Zr-GPF-MNPs reached 4.83 ± 0.50% ID/g and 5.13 ± 0.38% ID/g, respectively. Blocking experiments further confirmed the FAP-dependent targeting ability. Neither of the two nanoprobes elicited observable adverse effects in vivo. In conclusion, the FAPI-MNPs-based nanoprobe platform, which integrates active targeting and passive accumulation, improves tumor uptake and retention time of FAP-targeted radioligands with excellent biosafety. This study offers a new strategy and platform for the development of FAP-targeted diagnostic and therapeutic probes with promising clinical translation potential.
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DOI
PubMed
高影响因子
TENSIDE SURFACTANTS DETERGENTS
·
2025
·
IF 1.2
Wenwei Wu,Wenhuan Huang,Zhiguo Sun,Yuqin Tian,Yangwen Zhu,Quan Shi,Zhen Tao,Qingchun Deng,Haoye Cui,Bingang Chen,Yaoguo Wang,Bo Yu
Emerging carbon capture, utilization, and storage (CCUS) technologies have driven the development of advanced nanocomposite materials. In this study, a novel polyhedral oligomeric silsesquioxane (POSS)-based nanomaterial, referred to as FAP, was synthesized using acrylamide, sodium α-olefin sulfonate, and tea saponin as monomers. The structure of the material was confirmed by transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and silicon nuclear magnetic resonance spectroscopy ( 29 Si NMR), revealing a well-defined cage-like cubic architecture. TEM images clearly displayed the cage-like structure of the POSS material in FAP, while energy dispersive spectroscopy (EDS) confirmed the presence of silicon (Si) elements. Thermogravimetric analysis (TGA) showed that the incorporation of POSS materials improved the thermal resistance of FAP. The nanomaterials significantly improved the foaming performance and foam stability. The foam generated by FAP reached a height of 480 mL, with a half-life of 10 h under conditions of 120 °C and a salinity of 100,000 mg L −1 , showing excellent properties. Furthermore, the foam was regenerable in the presence of 20 % kerosene and maintained good foaming performance. Microscopic mechanism analysis indicated that the POSS nanomaterials compressed the electrical double layer of the polymer, reduced the particle size, increased the liquid film thickness, and markedly improved the foam stability. Under the influence of activators, the gel viscosity of FAP exceeded 100 mPa s, which significantly improved the underground sealing efficiency of CO 2 . The novel nanocomposite material exhibited integrated capabilities for CO 2 foaming, foam stabilization, and storage. The optimal concentration of the FAP foaming agent was 0.75 %, resulting in a 32.75 % increase in recovery efficiency, a resistance factor of 18.9, and a CO 2 storage rate of 12.59 %. The development of this nanocomposite material provides technological support for effectively mitigation of CO 2 channeling during CO 2 flooding and promotes the wider application of CO 2 flooding technology.
研究领域:
材料科学
·
环境科学
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DOI
高影响因子
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
·
2024
·
IF 8.6
Song Yangmeihui,Qin Chunxia,Chen Yixiong,Ruan Weiwei,Gai Yongkang,Song Wenyu,Gao Yu,Hu Wenzhu,Qiao Pengxin,Song Xiangming,Lv Xiaoying,Zheng Danzha,Chu Huikuan,Jiang Dawei,Yang Ling,Lan Xiaoli
Purpose The reversibility of early liver fibrosis highlights the need for improved early detection and monitoring techniques. Fibroblast activation protein (FAP) is a promising theranostics target significantly upregulated during fibrosis. This preclinical and preliminary clinical study investigated a FAP-targeted probe, gallium-68-labeled FAP inhibitor 04 ([ 68 Ga]Ga-DOTA-FAPI-04), for its capability to visualize liver fibrosis. Methods The preclinical study employed [ 68 Ga]Ga-DOTA-FAPI-04 micro-positron emission tomography (PET)/computed tomography (CT) on carbon tetrachloride-induced mice model (n = 34) and olive oil-treated control group (n = 26), followed by validation of the probe's biodistribution. Hepatic uptake was correlated with fibrosis and inflammation levels, quantified through histology and serum assays. FAP and α-smooth muscle actin expression were determined by immunohistochemistry, as well as immunofluorescence. The subsequent clinical trial enrolled 26 patients with suspected or confirmed liver fibrosis to undergo [ 68 Ga]Ga-DOTA-FAPI-04 PET/magnetic resonance imaging or PET/CT. Key endpoints included correlating [ 68 Ga]Ga-DOTA-FAPI-04 uptake with histological inflammation grades and fibrosis stages, and evaluating its diagnostic and differential efficacy compared to established serum markers and liver stiffness measurement (LSM). Results [ 68 Ga]Ga-DOTA-FAPI-04 mean uptake in mice livers was notably higher than in control mice, increasing from week 6 [0.70 ± 0.11 percentage injected dose per cubic centimeter (%ID/cc)], peaking at week 10 (0.97 ± 0.15%ID/cc) and slightly reducing at week 12 (0.89 ± 0.28%ID/cc). The hepatic biodistribution and FAP expression showed a consistent trend. In the patient cohort, hepatic [ 68 Ga]Ga-DOTA-FAPI-04 uptake presented moderate correlations with inflammation grades (r = 0.517 to 0.584, all P < 0.05) and fibrosis stages (r = 0.653 to 0.698, all P < 0.01). The average SUVmax to background ratio in the liver showed superior discriminative ability, especially between stage 0 and stage 1, outperforming LSM (area under curve 0.984 vs. 0.865). Conclusion [ 68 Ga]Ga-DOTA-FAPI-04 PET shows significant potential for non-invasive visualization and dynamic monitoring of liver fibrosis in both preclinical experiment and preliminary clinical trial, especially outperforming other common clinical indicators in the early stage. Trial registration NCT04605939. Registered October 25, 2020, https://clinicaltrials.gov/study/NCT04605939
研究领域:
医学影像学
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肝脏病学
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分子影像学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Songtao Li,Tianxing Lv,Xiaxia Fan,Mangmang Feng,Meng Zhou,Zhuoyu Li
Background Chemotherapy remains the main treatment for colon cancer, but the development of resistance has limited its efficacy. There is an urgent need to exploit a more effective therapeutic strategy. Alpha-linolenic acid (ALA), as an essential nutrient for the human body, has been found to increase the therapeutic effect of chemotherapy drugs. Purpose Exploring the potential mechanism of alpha linolenic acid reversing chemotherapy resistance in colon cancer. Results ALA reverses chemoresistance in colorectal cancer and suppresses stemness in resistant colorectal cancer cells. SPP1 functions as a key mediator in ALA-induced reversal of chemoresistance; its downregulation disrupts the interaction with the downstream receptor CD44, thereby mitigating chemotherapy resistance. Subsequently, ALA inhibits the expression of SOX2, a transcription factor that promotes SPP1 transcription. Further analysis revealed that decreased SPP1 expression leads to reduced levels of FAP, a marker of cancer-associated fibroblasts (CAFs), and that a functional interaction exists between SPP1 and FAP. Interestingly, ALA disrupted the interaction between SPP1 and FAP, thereby preventing CAFs accumulation. In vivo studies confirmed that ALA reverses colorectal cancer chemoresistance via the SOX2/SPP1/FAP signaling axis. Conclusion The study demonstrates that ALA in quinoa depresses the stemness of colorectal cancer and reduces the number of CAFs via SPP1, thereby reversing chemotherapy resistance. These findings highlight ALA as a promising dietary-based adjuvant for enhancing chemotherapy efficacy in colorectal cancer and provide new mechanistic insights into targeting tumor stemness and stromal remodeling.
研究领域:
肿瘤学
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分子生物学
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营养与癌症
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转化医学
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肿瘤微环境
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干细胞生物学
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产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2025
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IF 14.6
Danni Li,Xingyu Liu,Yanhong Wang,Boyu Cai,Chao Cheng,Changjing Zuo,Fei Tan
Cancer-associated fibroblasts (CAFs) are crucial in tumor progression and treatment resistance. Fibroblast activation protein (FAP) is an important molecular target in nuclear medicine for cancer diagnosis and therapy. Through comprehensive bioinformatic analysis and experimental validation, FAP was identified as a potential regulator of ferroptosis in CAFs. In this study, we developed a targeted radionuclide therapy (TRT) using a novel radiopharmaceutical, 131 I-labeled FAP inhibitor ( 131 I-FAPi), to specifically target CAFs and induce ferroptosis. Mechanistically, 131 I-FAPi TRT triggered three synergistic pathways. First, β -radiation-mediated water radiolysis generated hydrated electrons (e aq - ), which drove the conversion of Fe 3+ to Fe 2+ , disrupting iron homeostasis. Second, β -radiation-mediated water radiolysis produced primary ROS, providing an oxidative stress source promoting lipid peroxidation. Third, 131 I-FAPi TRT suppressed the expression of key antioxidant proteins SLC7A11 and GPX4, weakening the antioxidant defenses of CAFs. Furthermore, the study demonstrated that the combination of 131 I-FAPi TRT with cold atmospheric plasma (CAP) treatment significantly enhanced ferroptosis through efficient Fenton reaction activation. This study revealed the mechanism of β -radionuclide therapy in modulating cellular redox status and iron metabolism and provided a rational basis for developing combination therapies, such as TRT with CAP, to overcome treatment resistance and improve cancer outcomes.
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高影响因子
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