CERAMICS INTERNATIONAL
·
2023
·
IF 5.2
Xinwen Liu,Bingchu Mei,Guolong Tan
Given the downsizing and high integration of laser diodes in recent decades, Yb: Sr 5 (PO 4 ) 3 F (S-FAP) crystal materials are predicted to be employed as an all-solid laser medium to produce more energy for inertial nuclear fusion. The effects of various sintering conditions on the microstructure evolution and properties of 2 at. % Yb: S-FAP transparent ceramics by hot pressing sintering were systematically investigated in this work, which including sintering temperature , sintering pressure, heating rate, and holding time. When other sintering variables are held constant, the results reveal that a sintering temperature of up to 1050 °C results in visible grain development, substantial optical scattering, and even a significant carburizing impact at 1100 °C. Excessive sintering dwell time will result in grain development, and a high sintering holding time will result in the emergence of intergranular pores, lowering the optical quality of ceramics. The optimal heating rate range for as-synthesized ceramic is found to be 5–15 °C/min. Moreover, the grain development process of Yb: S-FAP transparent ceramics is determined to be grain boundary diffusion, with an activation energy of 239.4 kJ/mol during hot pressing sintering. Meanwhile, the as-prepared sample has excellent mechanical properties such as Vickers hardness of 7.47 ± 0.045 GPa, which are highly competitive when compared to other Yb-doped optical ceramic media such as Y 2 O 3 , YAG, Lu 2 O 3 , and so on. Finally, the transmittance was interpreted based on the microstructures of the as-synthesized ceramic samples and the Rayleigh-Gans-Debye scattering theory.
研究领域:
材料科学
·
光学工程
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DOI
高影响因子
ACS Applied Materials & Interfaces
·
2026
·
IF 7.8
Li Xiang,Jiachi Xu,Yukang Lin,Xianjing Xiang,Qiangqiang Jiao,Sainan Zhu,Wenhui Zhang,Yuting Qin,Yuping Chen
Fibrotic tumor microenvironment driven by activated hepatic stellate cells (aHSCs) and cancer-associated fibroblasts poses a formidable challenge to antitumoral drug delivery in hepatocellular carcinoma (HCC) by promoting angiogenesis, immunosuppression, and dense extracellular matrix barrier. Overcoming this fibrosis-associated delivery resistance requires nanotherapeutic systems to not only target the stromal compartment but also adapt their structure within the tumor matrix to improve deep penetration. Herein, we report a fibroblast activation protein-α (FAP-α)-responsive, size-transformable lipid nanoparticle platform with integrated stromal targeting, enzymatic activation, and intracellular delivery capacity for enhanced drug penetration and stromal remodeling in fibrotic HCC. This developed system, denoted as SOR/DOX@GPA-LNP, is co-loaded with sorafenib and doxorubicin and engineered with three key features: (i) a FAP-α-cleavable GPA peptide linker for TME-specific activation, (ii) FAP-α-mediated targeting of aHSCs, and (iii) a PAMAM core-mediated proton sponge activity to facilitate endosomal escape. Physicochemical characterization demonstrates that GPA-LNPs possess uniform size distribution, high colloidal stability, pH-responsive release behavior, and favorable heme- and cyto-compatibility. In vitro studies confirmed their selective aHSC-targeting ability, while in vivo imaging showed enhanced accumulation and retention in nude mice bearing subcutaneous tumors and orthotopic tumor-bearing mice. GPA-LNPs exhibited size reduction (from 170.5 to 146.3 nm) upon exposure to FAP-α, which significantly improved transport in three-dimensional HCC/aHSC spheroid models and increased deeper intratumoral accumulation. This size-transformable property establishes a direct structure–property–function relationship linking FAP-α enzymatic responsiveness with enhanced stromal penetration. Functionally, SOR/DOX@GPA-LNPs simultaneously suppressed aHSC activation, disrupted the fibrotic stromal barrier, and delivered cytotoxic agents to tumor cells. In the orthotopic HCC model, SOR/DOX@GPA-LNPs achieved superior antitumor efficacy, improved stromal remodeling and reduced systemic toxicity compared to nonresponsive counterparts. Overall, this work presents a versatile strategy that couples TME-responsive size adaptability with dual-action payloads, offering a compelling approach to navigate the complexities of fibrotic HCC therapy.
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2026
·
IF 4.5
Luoxia Liu,Shujie He,Zeyuan Huang,Dongdong Wang,Jianyuan Zhou,Jingfei Yang,Yifan Shi,Zhaoting Cheng,Siyuan Cheng,Sijuan Zou,Jun Zhao,Xiaohua Zhu
Most studies on fibroblast activated protein (FAP)-targeted radiopharmaceuticals focus on administered radioactivity, often overlooking the impact of a molar dose on tumor-targeting and off-target accumulation. Here, we investigate the effect of molar dose on biodistribution and pharmacokinetics using [68Ga]Ga-FAPI-04 PET and systematically evaluated two FAP-targeted dimers, DOTAGA.(SA.FAPi)2 and DOTAGA.Glu.(FAPi)2, in a 4T1 syngeneic tumor model. Dynamic PET imaging confirmed a clear molar dose-dependent effect on tumor uptake, tumor-to-organ ratios, and organ pharmacokinetics with lower molar doses prolonging tumor retention. Comparative analyses across multiple molar doses revealed that DOTAGA.Glu.(FAPi)2 achieved comparable tumor uptake to DOTAGA.(SA.FAPi)2 but exhibited significantly reduced liver accumulation. An optimal molar dose range of 8–32 nmol/kg was identified, balancing maximal tumor uptake with reduced off-target exposure. At this optimized dose, [177Lu]Lu-DOTAGA.Glu.(FAPi)2 demonstrated therapeutic efficacy in 4T1 tumor-bearing mice with limited systemic toxicity. These results establish molar dose optimization as a broadly applicable strategy for accurately evaluating and comparing FAP-targeted radiopharmaceuticals and provide a methodological framework to guide future preclinical development and translational studies.
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DOI
PubMed
高影响因子
Materials Today Bio
·
2026
·
IF 11
Yangmengyuan Xu,Yiqing Zhang,Zijie Sun,Junfeng Gong,Qi Shen,Hao Meng,Xi Liu,Junli Chen,Yaying Hao,Zhan Xu,Kui Ma,Liqian Ma,Kailu Guo,Xiaohua Pan,Xiaobing Fu,Cuiping Zhang
Hypertrophic scars (HS) lack cell-specific therapies because pathogenic hypertrophic scar fibroblasts (HSFs) are hard to inactivate without damaging human dermal fibroblasts (HDFs). Ferroptosis has emerged as a potential antifibrotic vulnerability of activated fibroblasts, yet its translational use is constrained by off-target toxicity of small-molecule inducers. Here, we report a targeted delivery strategy based on small extracellular vesicles (sEVs) surface-decorated with a fibroblast activation protein (FAP) ligand to preferentially deliver a widely used ferroptosis inducer erastin to HSFs. We confirmed that FAP is upregulated in HSFs and HS tissue, and engineered adipose-derived mesenchymal stem cell (ADSC)-derived sEVs loaded with erastin and covalently conjugated with the FAP ligand UAMC1110 (sEVs ErF ) via EDC/NHS chemistry. sEVs ErF retained typical nanoscale characteristics and EV marker profiles and showed preferential uptake by HSFs over HDFs in vitro , which was validated by competitive blocking and FAP knockdown experiments. Functionally, sEVs ErF suppressed HSF proliferation and migration and reduced α-SMA, COL I, and COL III expression, accompanied by ferroptosis-associated signatures including lipid peroxidation, glutathione depletion, labile Fe 2+ accumulation, and mitochondrial dysfunction. For localized dermal delivery, sEVs ErF were incorporated into dissolvable microneedle patches (DMNPs) with GelMA tips and a PVA backing. In a rabbit ear HS model, sEVs ErF -DMNPs reduced scar thickness and collagen deposition and modulated ferroptosis- and fibrosis-related readouts in scar tissues. Both in vitro and in vivo rescue experiments using the ferroptosis inhibitor Ferrostatin-1 confirmed that these effects were specifically mediated by ferroptosis. Collectively, these results support FAP as an actionable targeting handle for preferential delivery to scar fibroblasts and suggest that ferroptosis-associated inactivation of HSFs can be leveraged through a microneedle-enabled, locally retained sEV formulation.
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DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Pei Wang,Shuailiang Wang,Futao Liu,Ya’nan Ren,Qian Guo,Qian Zhang,XingGuo Hou,Yuan Yao,Hua Zhu,Zhi Yang
Prostate-specific membrane antigen (PSMA) is a prostate cancer target that plays a crucial role in prostate cancer diagnosis and therapy. Herein, a novel dual-targeted imaging probe, [68Ga]Ga-FAPI-PSMA, was prepared by radiolabeling conjugated DOTA-FAPI-PSMA with the short half-life radionuclide gallium-68 (68Ga), which is dedicated to prostate cancer diagnostic imaging. In vitro, [68Ga]Ga-FAPI-PSMA had higher affinity for the PSMA and FAP high-expressing cell lines 22Rv1 and U87 MG with IC50 values of 4.73 and 2.10 nM, respectively, than in the corresponding negative expression cell lines PC3 and A549, and significant differences in cell uptake were also observed. In vivo, [68Ga]Ga-FAPI-PSMA was rapidly cleared from the body, and the estimated radiation dose was relatively low compared with several other FAPI probes. In 22Rv1 and U87 MG tumor xenografts, [68Ga]Ga-FAPI-PSMA rapidly accumulated in tumors after administration, and the best images can be obtained at 1 h postinjection. In conclusion, the dual-targeted probe [68Ga]Ga-FAPI-PSMA was successfully prepared for in vivo prostate cancer PET/CT imaging.
研究领域:
放射学
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肿瘤学
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分子影像
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核医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY
·
2025
·
IF 1.6
Su Dongping,Liao Yuhao,Wang Jieru,Liu Ruomeng,Cai Huawei,Yin Xiaojie,Qin Zhi,Zhang Jinsong,Yao Zeen,Li Bo
To evaluate the suitability of 47 Sc for SPECT imaging and therapeutic effect, a fibroblast activation protein (FAP) inhibitor FAPI-46 was used for cancer theranostics in preclinical setting. 47 Sc was successfully produced via thermal neutron irradiation of 46 Ca and then conjugated with FAPI-46, achieving a high radiochemical purity over 98%. In vitro experiments confirmed the FAP mediated specific binding to MG-63 cells for 47 Sc-FAPI-46. Biodistribution and SPECT/CT imaging indicated specific uptake of 47 Sc-FAPI-46 in PANC-2 pancreatic tumors. Therapeutic experiments revealed an effective anti-tumor ability with negligible toxicity of 47 Sc-FAPI-46 in xenografted tumor mice.
研究领域:
核医学
·
放射性药物化学
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肿瘤学
·
分子成像
·
诊疗一体化
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DOI
高影响因子
Theranostics
·
2025
·Vol. 15
·期 9
·3877
·
IF 13.3
Yueyang Li,Yu Zhai,Tianling Wang,Siya Wang,Yu Tian,Zhiqun Bian,Yang Zhang,Chao Zhang,Minghan Liu,Changqing Li
Rationale: Nucleus pulposus (NP) fibrosis is a contributing factor to intervertebral disc degeneration (IVDD), which lacks an effective treatment. This study focuses on elucidating the role and mechanisms of the TGF-β signaling repressor SKI in NP fibrosis and exploring its therapeutic potential. Methods: Single-cell RNA sequencing (scRNA-seq) was used to investigate fibrotic nucleus pulposus cell (NPC) subsets and assess TGF-β signaling activation. Two recombinant plasmids encoding single-chain variable fragments (scFvs) targeting the fibrotic NPC marker FAP and SKI mRNA were co-transfected into HEK-293T cells to yield functionalized exosomes (EX ski+scFv ). The addition of EX ski+scFv to a gelatin/oxidized sodium alginate hydrogel produced a pH-responsive exosome/hydrogel system named Gel@EX ski+scFv . The therapeutic effects and underlying mechanism of Gel@EX ski+scFv were evaluated by RNA sequencing, molecular docking and coimmunoprecipitation. Results: A fibrotic NPC subset was characterized by elevated FAP and diminished SKI expression, along with activation of the TGF-β signaling pathway. SKI overexpression reduced fibrosis in TGF-β-treated NPCs. EX ski+scFv successfully delivered SKI mRNA to FAP-expressing fibrotic NPCs. Gel@EX ski+scFv possessed good mechanical properties, degradability, injectability, and biocompatibility. Gel@EX ski+scFv effectively alleviated NP fibrosis and IVDD in rats. RNA sequencing, molecular docking and coimmunoprecipitation revealed that SKI could interact with FOXO3 to suppress the TGF-β signaling pathway. Conclusion: This study elucidates the mechanism by which SKI -mediated TGF-β signaling inhibition alleviates NP fibrosis. The development of the Gel@EX ski+scFv system for the targeted delivery of SKI mRNA offers a promising therapeutic strategy to alleviate NP fibrosis and IVDD in the future.
研究领域:
生物医学
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分子生物学
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组织工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG TARGETING
·
2024
·
IF 4.3
Mingli Sui,Chaoqun Wang,Yingmei Tian,Huijuan Zhang
Phototherapy can cause autophagy while killing tumour cells, leading to tumour recurrence and metastasis. Here, we constructed a laser and enzyme dual responsive nanodrug delivery system Tf-Te@CTSL-HCQ (TT@CH) to precisely regulate autophagy in synergy with phototherapy to inhibit the proliferation and metastasis of melanoma. Firstly, transferrin (Tf) was used as a nanoreactor to synthesise phototherapy agent Tf-Te by the biological template mineralisation method. Then, the thermosensitive liposome modified with FAP-α-responsive peptide (CAP) was used as a carrier to encapsulate autophagy inhibitor hydroxychloroquine (HCQ) and Tf-Te, to obtain an intelligent TT@CH delivery system. Once arriving at the tumour site, TT@CH can be cleaved by FAP-α overexpressed on cancer-associated fibroblasts (CAFs), and release Tf-Te and HCQ. Then Tf-Te can target melanoma cells and exert PTT/PDT anti-tumour effect. What’s more, hyperpyrexia induced by PTT can further promote drugs release from TT@CH. Meanwhile, HCQ simultaneously inhibited autophagy of CAFs and melanoma cells, and down-regulated IL-6 and HMGB1 secretion, thus effectively inhibiting melanoma metastasis. Pharmacodynamic results exhibited the best anti-tumour effect of TT@CH with the highest tumour inhibition rate of 91.3%. Meanwhile, lung metastatic nodules of TT@CH treated mice reduced by 124.33 compared with that of mice in control group. Overall, TT@CH provided an effective therapy strategy for melanoma.
研究领域:
肿瘤学
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药学
·
纳米技术
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Dinghu Weng,Rong Guo,Changling Dong,Yuan Luo,Dasheng Qiu,Liying Xu,Guobin Xu
The aim of this study was to synthesize a quinoline-based MRI contrast agent, Gd-DOTA-FAPI04, and assess its capacity for targeting fibroblast activation protein (FAP)-positive tumors in vivo. Gd-DOTA-FAPI04 was synthesized by attaching a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) complex of gadolinium(III) to FAP inhibitor FAPI04. The longitudinal relaxation time (T1) of the contrast agent was measured using a Siemens Prisma 3.0T MR system, and the CCK-8 assay was performed to evaluate its potential cytotoxicity. Male nude mice bearing tumors grown from FAP-expressing fibrosarcoma cells were divided into experimental (n = 4) and control (n = 4) groups, and T1-weighted image enhancement was measured at different times (0, 10, 30, 60, 90, and 120 min) postinjection of Gd-DOTA-FAPI04. The control group received an additional preinjection of excess FAPI04. FAP expression in tumor tissue was investigated by using immunohistochemistry with an anti-FAP antibody. The longitudinal relaxivities of gadodiamide and Gd-DOTA-FAPI04 were measured to be 3.734 mM–1 s–1 and 5.323 mM–1 s–1, respectively. The CCK-8 assay demonstrated that Gd-DOTA-FAPI04 has minimal toxicity to cultured human fibrosarcoma cells. In vivo MRI showed that peak accumulation of Gd-DOTA-FAPI04 in FAP-expressing tumors occurred 1 h postinjection and could be blocked by preinjection of excess FAPI04. Immunohistochemical analysis of harvested tumor tissue supported the above findings. Gd-DOTA-FAPI04 is a promising contrast agent for in vivo imaging of FAP.
研究领域:
医学成像
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肿瘤学
·
药物化学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Ya Ren,Weiqing Kong,Yihao Liu,Xue Yang,Xiang Xu,Lei Qiang,Xuelian Mi,Changru Zhang,Haoyi Niu,Chengwei Wang,Jinwu Wang
Bone defect repair remains a major clinical challenge that requires the construction of scaffolds that can regulate bone homeostasis. In this study, a photo-cured mesoporous bioactive glass (PMBG) precursor is developed as a tricalcium phosphate (TCP) agglomerant to obtain a double-phase PMBG/TCP scaffold via 3D printing. The scaffold exhibits multi-scale porous structures and large surface areas, making it a suitable carrier for the loading of parathyroid hormone (PTH) (1-34), which is used for the treatment of osteoporosis. In vitro and in vivo results demonstrate that PMBG/TCP scaffolds coordinated with PTH (1-34) can regulate bone homeostasis in a bidirectional manner to facilitate bone formation and inhibit bone resorption. Furthermore, bidirectional regulation of bone homeostasis by PTH (1-34) is achieved by inhibiting fibrogenic activation protein (FAP). Thus, PMBG/TCP scaffolds coordinated with PTH (1-34) are viable materials with considerable potential for application in the field of bone regeneration and provide an excellent solution for the design and development of clinical materials.
研究领域:
生物医学工程
·
材料科学
·
再生医学
·
骨科
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Xinyuan Zhou,Pan Zhang,Nan Liu,Xiao Zhang,Hui Lv,Wei Xu,Meirong Huo
Pancreatic cancer (PC) carries a poor prognosis among all malignancies and poses great challenges to clinical drug accessibility due to the severely fibrotic and hypoxic tumor microenvironment (TME). Therein, cancer-associated fibroblasts (CAFs), which are extremely abundant in PC, play a key role in forming the complex PC microenvironment. Therefore, a highly efficient TME reprogramming therapeutic paradigm that can specifically inhibit CAF function is urgently needed. Herein, we successfully developed a novel CAF-tailored nanosystem (Dex-GP-DOCA, DPD) loaded with a potent anti-fibrosis flavonoid compound (Quercetin, QUE), which possesses biological responsiveness to fibroblast activation protein alpha (FAP-α), prolonged TME remodeling and enhancement of clinical chemotherapeutics. Specifically, DPD/QUE allowed for extracellular matrix (ECM) reduction, vessel normalization, hypoxia-induced drug resistance reversal, and blockade of Wnt16 paracrine in CAFs. More importantly, this chemotherapy conducive microenvironment persisted for at least 8 days following treatment with DPD/QUE. It should also be noted that the effective and prolonged microenvironment modulation induced by DPD/QUE significantly improved the chemotherapy sensitivity of Abraxane and gemcitabine, the first-line chemotherapeutic drugs for PC, with inhibition rates increasing from 37.5% and 40.0% to 87.5% and 85.2%, respectively. Overall, our CAFs-targeted nanosystem showed promising prospects for remodeling the TME and facilitating chemotherapy for refractory pancreatic cancer.
研究领域:
肿瘤学
·
药理学
·
纳米技术
·
癌症生物学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
Jing Yan,Qinghua Wu,Ziyin Zhao,Jianhua Wu,Huan Ye,Qiujun Liang,Zhuchao Zhou,Mengying Hou,Xudong Li,Yong Liu,Lichen Yin
The anticancer performance of nanomedicine is largely impeded by insufficient intratumoral penetration. Herein, tumor microenvironment (TME)-amendatory and self-adaptive nanoclusters (NCs) capable of cancer-associated fibroblasts (CAFs) depletion and size/charge conversion were engineered to mediate light-assisted, hierarchical intratumoral penetration. Particularly, large-sized NCs (~50 nm) were prepared via self-assembly of FAP-α-targeting peptide-modified, 1 O 2 -sensitive polymers, which were further used to envelope small-sized dendrimer (~5 nm) conjugated with Ce6 and loaded with DOX (DC/D). After systemic administration, the NCs efficiently targeted CAFs and generated lethal levels of 1 O 2 upon light irradiation, which depleted CAFs and concomitantly dissociated the NCs to liberate small-sized, positively charged DC/D. Such stroma attenuation and NCs transformation collectively facilitated the delivery of DC/D into deeper regions of CAF-rich tumors, where DOX and 1 O 2 provoked synergistic anti-cancer efficacies. This study provides an effective approach to facilitate the tumor penetration of nanomedicine by concurrently and spatiotemporally reconfiguring the nano-properties and remodeling the TME.
研究领域:
纳米技术
·
癌症治疗
·
药学
·
生物医学工程
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）