JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Yan Chen,Shuaiqi Feng,Lanjie Li,Guiqin Liu,Qingshan Ma,Zhifang Liu,Yanna Zhao,Qingpeng Wang
Grapefruit extracellular vesicle (GEVs) derived nanodrug Tf-GEVs@Pt(IV) loading novel three-functional platinum(IV) conjugates was developed, which was effective in modulating the inflammatory, fibrotic, and immunosuppressive tumor microenvironment (TME). The GEVs enhanced the penetration of Tf-GEVs@Pt(IV) into tumor tissues, while the transferrin (Tf) moiety further improved the tumor-targeting capabilities. The active ingredient, platinum(IV) conjugate, was released in a sustained manner within the TME, which was easily reduced to platinum(II), aspirin (ASP), and captopril (CTP) fragments. The platinum core caused significant DNA damage. The inflammatory TME was ameliorated by inhibiting COX-2 and reducing TNF-α and IL-6 through the synergistic actions of GEVs and ASP. Collagen fibrosis was disrupted by the CTP moiety, which downregulated TGF-β1, MMP2, and MMP9. Consequently, the immunologically ‘cold’ TME was transformed into a ‘hot’ state by inhibiting PD-L1 and activating cGAS/STING pathways. Then, the T-cell activation and macrophage polarization from the M2- to M1-phenotype were provoked in tumor tissues.
研究领域:
药理学
·
肿瘤学
·
纳米医学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Gao He,Xiafei Yu,Junzhe Yang,Lile Dong,Jialu Xu,Xian Wu,Xiang Li,Xiaoan Liu
Ferroptosis has emerged as a promising strategy for enhancing tumor immunogenicity. However, a major obstacle to the efficacy of ferroptosis-based immunotherapy is the immunosuppressive tumor microenvironment, particularly the dominance of tumor-associated macrophages (TAMs) exhibiting the M2 phenotype. These M2 macrophages secrete immunosuppressive factors, limiting the therapeutic potential of ferroptosis. To overcome these challenges, hollow Te/PtTe 2 inducers were designed to enhance immunotherapy induced by ferroptosis. The unique hollow structure of Te/PtTe 2 inducers effectively captures mechanical energy, promotes efficient electron-hole separation, and triggers reactive oxygen species (ROS) storms within tumor cells. Simultaneously, Te/PtTe 2 inducers synergistically deplete intracellular GSH in combination with ROS storm effects, triggering ferroptosis and releasing damage-associated molecular patterns, enhancing tumor immunogenicity. Additionally, Te/PtTe 2 inducers reshape the immunosuppressive microenvironment under US irradiation by increasing mature dendritic cells, promoting CD8 + T cell infiltration, and reducing immunosuppressive M2 macrophages. Collectively, this work provides a piezoelectric enhancement strategy to overcome immunosuppressive barriers and improve the clinical effectiveness of ferroptosis in cancer treatment.
研究领域:
生物医学
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肿瘤学
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免疫学
·
材料科学与医学应用
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Peiliang Zhong,Yuyue Zhao,Hao Cui,Guowang Cheng,Linze Xia,Zhen Tian,Wei Liu,Jiaxin Wu,Jiaxian Yu,Xinyi Peng,Guangtao Yu,Dandan Ma
The hypoxia-induced immunosuppressive tumor microenvironment (TME) significantly limits the effectiveness of various solid tumor therapies. In this study, we developed a biomimetic photosynthetic nanoreactor system, termed Met-Tk-PLGA (MTP), by incorporating thylakoid membranes (Tk-M) with PLGA microspheres encapsulating metformin (Met). This system generates oxygen (O 2 ) in situ within the TME via photosynthesis while releasing Met to reduce cellular O 2 consumption, thereby alleviating tumor hypoxia. In vitro experiments confirmed that the Tk-M of MTP produces substantial O 2 via photosynthesis and, in combination with Met, significantly suppressed hypoxia-related signaling pathway protein expression. In vivo studies using an oral squamous cell carcinoma (OSCC) mouse model demonstrated that this combination therapy inhibited tumor growth and reversed hypoxia-induced immunosuppression in the TME, thereby enhancing antitumor immune responses. This dual strategy, alleviating tumor hypoxia through Tk-M−mediated O 2 generation and Met-induced reduction in O 2 consumption, offers a promising therapeutic approach to address tumor hypoxia.
研究领域:
肿瘤学
·
生物医学工程
·
药理学
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产品关联
DOI
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2013
·Vol. 66
·期 4
·557-563
·
IF 2.033
Zhang Zhaoliang,Xu Lu,Chen Hao,Li Xingyi
ObjectivesAllograft rejection is the major cause of corneal graft failure. To inhibit corneal allograft rejection, rapamycin as a novel immunosuppressive agent has been discovered. However, the high water insolubility and low bioavailability of rapamycin has strongly hindered its application in the clinical setting. In this paper, we attempted to develop a novel rapamycin nano-formulation using poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCEC) nanoparticles as carrier by an emulsion evaporation method for potential application in corneal transplantation.MethodsThe solubility of rapamycin in the nano-formulation was determined and in-vitro release studies were performed. The developed rapamycin-loaded PCEC nanoparticles were further characterized by dynamic light scattering, transmission electron microscopy, X-ray diffraction and differential scanning calorimetery. Toxicity studies were performed in eye-related cell lines.Key findingsThe rapamycin in nano-formulation exhibited ∼103-fold increased solubility as compared with native rapamycin. According to the results of the in-vitro cytotoxicity assay, the developed PCEC nanoparticles did not exhibit any apparent cytotoxicity against various eye-related cell lines with PCEC nanoparticle concentrations in the range of 0.05–10 mg/ml. In-vitro release study showed that the release of rapamycin was sustained from PCEC nanoparticles over a period of 48 h.ConclusionsAll the results suggested that the developed rapamycin-loaded PCEC nanoparticles might be suitable for immunosuppression in corneal transplantation by instillation administration.
研究领域:
药剂学
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眼科医学
·
生物材料学
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DOI
高影响因子
Food & Function
·
2024
·
IF 5.1
Lei Zhong,Qiuhui Hu,Qiping Zhan,Mingwen Zhao,Liyan Zhao
Individuals with immune disorders cannot establish an adequate defense to pathogens, leading to gut microbiota dysbiosis. β-Carotene can regulate immune response, but its bioavailability in vivo is very low. Herein, we developed a glycosylated oat protein-based nanoparticle to improve the application of β-carotene for mitigating cyclophosphamide-induced immunosuppression and gut microbiota imbalance in mice. The results showed that the nanoparticles facilitated a conversion of β-carotene to retinol or retinyl palmitate into the systemic circulation, leading to an increased bioavailability of β-carotene. The encapsulated β-carotene bolstered humoral immunity by elevating immunoglobulin levels, augmenting splenic T lymphocyte subpopulations, and increasing splenic cytokine concentrations in immunosuppressed mice. This effect was accompanied by the alleviation of pathological features observed in the spleen. In addition, the encapsulated β-carotene restored the abnormal gut microbiota associated with immunosuppression, including Erysipelotrichaceae, Akkermansia, Bifidobacterium and Roseburia. This study suggested that nanoparticles loaded with β-carotene have great potential for therapeutic intervention in human immune disorders by specifically targeting the gut microbiota.
研究领域:
食品科学
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免疫学
·
微生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2025
·
IF 5.5
Jian Guo,Wen-Ping Lin,Tao Tang,Fushou Liu,Fangtao Tan,Longshua Qin,Wendi Xu,Hao Li,Zhi-Jun Sun,Ran Cui,Mingxi Zhang
The immunosuppressive tumor microenvironment (TME), characterized by elevated adenosine levels, poses a significant barrier to effective cancer immunotherapy. Herein, we report an ultrasound-activatable nanoprobe based on piezoelectric quantum dots (QDs) emitting in the near-infrared-IIb (NIR-IIb) window. The nanoprobe integrates a fluorescent QDs core with tumor-targeting peptides and CD73 inhibitors conjugated via a reactive oxygen species (ROS)-responsive linker. Attributed to the optimized piezoelectricity of the QDs core, this nanoprobe could generate ROS under deep-penetrating ultrasound irradiation. The bright NIR-IIb fluorescence and tumor-targeting ability enable the noninvasive delineation of the tumor margin from normal tissue, guiding the optimal scope and timing of ultrasound treatment. The precise ultrasound irradiation triggers the cleavage of the ROS-responsive linker and the release of the CD73 inhibitor, which effectively inhibits the production of adenosine in TME. This reduction alleviates immunosuppression and robustly activates antitumor immunity in mice, achieving significant therapeutic efficacy. This work provides a promising strategy for overcoming adenosine-mediated immunosuppression and advancing precise ultrasound therapy for cancers.
研究领域:
肿瘤学
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医学影像
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免疫治疗
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生物材料
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产品关联
DOI
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2025
·
IF 3.8
Shi Jianhua,Huang Jin,Qing Jiang,Chen Youwei,Meng Taoyu,Zhou Wenli,Xu Zhou,Chen Maolong,Wen Li,Jiao Ye,Cheng Yunhui,Wang Libing,Ding Li
Immunosuppressant drugs (ISDs) are widely used in the treatment of organ rejection following human transplantation and in autoimmune diseases. Herein, this study demonstrates that carbonylated covalent organic frameworks (COFs) with pore-matching capabilities can serve as promising interference-resistant adsorbents for the rapid and efficient capture of ISDs (cyclosporin A (CsA), tacrolimus (FK-506), and rapamycin (RPM)) from complex whole blood matrices. Under optimized conditions, MCOF-2-COOH, with a pore size 1.5 times the diameter of the drug molecule, demonstrated superior ISDs adsorption performance, achieving an adsorption capacity of up to 84.95 mg g −1 in 10 min. Instrumental characterization and theoretical calculations elucidated the potential adsorption matrix, revealing that the COF provides multiple forces, including hydrogen bonding, electrostatics, and π-π interactions, with the carboxyl site playing a crucial role. This study provides both a theoretical basis and experimental evidence for the use of COF materials in the selective adsorption of drugs from complex matrices, as well as a strategy for designing functionally customized COFs for drug therapy monitoring applications. Graphical
研究领域:
药物化学
·
材料科学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
Open Medicine
·
2023
·Vol. 18
·期 1
·
IF 2.1
Yangfa Chao,Wenting Huang,Zhiheng Xu,Ping Li,Shaodong Gu
Lymphocyte apoptosis is a latent factor for immunosuppression in sepsis. Forkhead box protein P3 (FOXP3) can interact with RUNX family transcription factor 1 (RUNX1) in regulatory T cells. Our research was to probe whether RUNX1/FOXP3 axis affects immunosuppression in the process of sepsis by modulating T and B lymphocyte apoptosis. We constructed sepsis model in mice and mouse CD4 + T and CD19 + B lymphocytes. RUNX1 and FOXP3 expressions and apoptosis in cells were assessed by western blot, quantitative real-time PCR, and flow cytometer. Inflammation of serum and pathological damage was assessed by ELISA and H&E staining. Relationship between RUNX1 and FOXP3 was assessed by co-immunoprecipitation. The findings showed that RUNX1 ameliorated the survival rate, pathological damage, and decreased inflammation-related factors, and inhibited apoptosis of CD4 + T and CD19 + B cells in cecal ligation and puncture mice. Furthermore, RUNX1 up-regulated the viability and down-regulated apoptotic rate with the changed expressions of apoptosis-related molecules in lipopolysaccharide (LPS)-mediated CD4 + T and CD19 + B cells. Additionally, FOXP3 interacted with RUNX1, and its silencing decreased RUNX1 expression and reversed the inhibitory effect of RUNX1 on apoptosis of LPS-mediated CD4 + T and CD19 + B cells. In summary, the RUNX1/FOXP3 axis alleviated immunosuppression in sepsis progression by weakening T and B lymphocyte apoptosis.
研究领域:
免疫学
·
分子生物学
·
病理学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2023
·
IF 5.9
Mingshi Deng,Wei Jin,Wenjuan Yang,Lingling Tian,Xinghua Gao,Xuefeng Wang,Lingyan Feng,Metini Janyasupab,Bingpu Zhou,Yuan Zhang
Mycophenolic acid (MPA), which is a potent immunosuppressant, has been widely used to prevent organ rejection after organ transplantation. In clinical practice, it is essential to monitor the free MPA concentration. Herein, convenient and fast electrochemical microsensing technology is developed for directly detecting the MPA concentration. To implement this method, ultrathin copper-based metal–organic framework (Cu–MOF) nanosheets with a thickness of about 6.6 nm are used to detect MPA. An analysis of electrochemical behavior reveals the direct electrochemical catalytic oxidation mechanism of MPA molecules on a Cu(II) tetrakis(4-carboxyphenyl)porphyrin (Cu–TCPP)-modified electrode. Furthermore, electrochemical testing results show that the ultrathin Cu–TCPP nanosheet-based microsensor exhibits high sensitivity and specificity for MPA in the nano- to micromolar range, with a detection limit of 10 nM. X-ray absorption spectroscopy (XAS) characterization reveals that the unsaturated metal ions in ultrathin nanosheets are the active sites responsible for boosting the catalytic oxidation of MPA molecules. High-performance liquid chromatography–tandem mass spectrometry further shows the catalytic oxidation product of MPA and that the phenolic hydroxyl group in the MPA molecule is the active site where the catalytic reaction occurs. The considerable sensing performance of the Cu–TCPP nanosheet-based microsensor proves that it is possible to develop a fast and convenient method for the direct high-frequency monitoring of immunosuppressive drugs.
研究领域:
分析化学
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生物医学工程
·
药物分析
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DOI
高影响因子
TALANTA
·
2025
·
IF 6.1
Yinqiang Xia,Jin Zhao,Zheying Gao,Yifei Ruan,Siqi Wang,Liangbin Hu,Tianli Yue
Matrix interference poses persistent and significant challenges against rapidly detecting gentamicin residue in foods. Here, we fabricated synergistic antifouling surfaces using the phase transition of bovine serum albumin (PTB) and hyaluronic acid (HA) on substrates. The hybrid PTB + HA coatings showed ultralow adsorption of BSA and lysozyme, requiring 10 times less PTB dosage. With PTB's assistance, the modification of HA proved to be much more cost-effective than the sulfhydrated HA. The adsorption of E. coli on the hybrid coatings could be reduced by 92.6 %, illustrating good properties of antibacterial adsorption. Furthermore, the hybrid surfaces demonstrated good stability despite being rinsed with strong acid and alkaline solutions. Based on the immune-inhibition assay, the sensitive antifouling sensors were developed with a low detection limit (1.8 ng/mL for gentamicin) and satisfactory recovery rate (94.0 %–104.0 %) in goat milk. All tests could be completed within 10 min, confirming the sensor system's feasibility and efficiency.
研究领域:
生物化学
·
材料科学
·
分析化学
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产品关联
DOI
PubMed
高影响因子
Science Bulletin
·
2024
·
IF 18.8
Xia Jie,Zhang Lixing,Zhu Wucheng,Tu Juchuanli,Peng Xilei,Deng Qiaodan,Li Siqin,He Xueyan,Dong Haonan,Liu Cuicui,Chen Xian,Xu Jiahui,Ma Wei,Xiao Yi,Liu Wen,Hu Guohong,Jiang Yi-Zhou,Chen Ceshi,Bian Xiu-Wu,Shao Zhi-Ming,Liu Suling
Neurotransmitters are increasingly recognized to play important roles in limiting anti-tumor immunity. N-acetyl-aspartyl-glutamate (NAAG) has been extensively studied in neurological disorders; however, its potential role in restricting anti-tumor immunity has not been investigated. Here, we demonstrated that NAAG or its synthetase RimK-like family member B (RIMKLB) significantly disrupted anti-tumor immunity by rewiring the myeloid progenitor differentiation of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), which in turn promoted breast cancer growth and metastasis. Mechanistically, NAAG sustained the tumor immunosuppressive microenvironment by activating an NR2B-containing NMDA receptor (NR2B-NMDAR)-dependent p38-NOTCH1 axis, and subsequently stimulating tumor cell migration and invasion, as well as inducing PMN-MDSC differentiation and expansion. In mouse models, RIMKLB ablation or NMDAR inhibition enhanced the efficacy of anti-PD-1 therapy and suppressed tumor progression. An analysis of clinical samples revealed that high levels of NAAG and NR2B-NMDAR predicted a poor prognosis in TNBC patients. Collectively, our findings have uncovered a signaling role for tumor-derived NAAG beyond its classic function as a neurotransmitter that can be targeted pharmacologically to enhance immunotherapy against breast cancer.
研究领域:
肿瘤学
·
免疫学
·
生物化学
·
分子生物学
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DOI
高影响因子
Nanoscale
·
2017
·Vol. 9
·期 37
·14236-14247
·
IF 7.367
Zhenzhen Wang,Yan Zhang,Zhen Liu,Kai Dong,Chaoqun Liu,Xiang Ran,Fang Pu,Enguo Ju,Jinsong Ren,Xiaogang Qu
Unmethylated cytosine-phosphate-guanine (CpG) oligonucleotides (ODNs) possess high immunostimulatory activity and represent attractive tools for cancer treatment. However, their success in eliminating large solid tumors was hampered by the immunosuppressive tumor microenvironment. Herein, we report that the design of a novel MnO2–CpG–silver nanoclusters (AgNCs)–doxorubicin (DOX) conjugate for enhanced cancer immunotherapy, in which MnO2 nanosheets function as unique supports to integrate the chemotherapy drug DOX and the immunotherapeutic agent CpG–AgNCs. Importantly, DOX could be conjugated with MnO2 nanosheets through π–π interactions to serve as a bifunctional modulator of the tumor microenvironment to activate a tumor-specific immune response by inducing immunogenic cell death, and reverse the immunosuppressive tumor microenvironment via abrogating the immune-suppressive activity of regulatory T cells, both of which would greatly improve the immune response of CpG–AgNCs. In this way, the T-cell immune responses of CpG–AgNCs which are linked to MnO2 nanosheets were significantly enhanced and could exhibit remarkable antitumor activity against large solid tumors. Our study may guide the rational design of immunotherapeutic boosters for improving cancer treatment.
研究领域:
肿瘤学
·
纳米医学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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