ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Yuanyuan Wen,Kaiming Li,Mengnan Ni,Hui Jiang,Haisi Wu,Qinqi Yu,Jinyu Li,Xiaolin Li,Jifu Wei,Wei Wu,Huae Xu
Recently, paclitaxel (PTX) was reported to increase intracellular lipid reactive oxygen species (ROS) levels, triggering cancer cell ferroptosis. Based on this, some efforts had been made to improve PTX treatment for non-small-cell lung cancer (NSCLC). Our previous studies demonstrated that triptolide (TPL) could improve the antitumor effect of PTX. Nevertheless, the poor solubility and side effects often limit the application of chemotherapy drugs. In this paper, we constructed a novel nanodrug delivery system (NDDS) chemosynthesis by PEGylated generation 3 (G3) dendritic polylysine coloaded with PTX and TPL (PTX-TPL-PEG-PLL, PTPP), which was endowed with the ability of tumor targeting and favorable solubility. In addition, we demonstrated that TPL could induce ROS generation by regulating the NF-κB signaling pathway to enhance the ferroptosis-induced effect of PTX. Besides, ferroptosis induced by PTPP could improve chemoresistance through inhibiting the level of P-gp, GPX4, and SLC7A11. Furthermore, we determined that ferroptosis may strengthen the immune response by increasing the expression of CD8+ T cells and IFN-γ+ cells while decreasing Treg cells. In general, PTPP may be a potential system for NSCLC treatment.
研究领域:
肿瘤学
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药理学
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纳米技术
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免疫学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Zhenying Diao,Youcheng Liang,Yong Liu,Dou Zhang,Long Qiu,Jianbo Sun,Qiaoyou Lu,Yanlei Liu,Daxiang Cui,Ting Yin
Blockade of heat shock protein 90 (HSP90) expression in multimodal synergistic therapy has a great prospect for cancer treatment. Nanomaterials combined with bioinformatic analysis provides accurate guidance for the design of anti-HSP90 nanomedicines. Herein, a NIR-II-responsive nanoplatform was developed under bioinformatics guided to effectly inhibit HSP90 for enhanced synergistic mild-photothermal chemotherapy without any notable tissue damage. The nanoplatforms were assembled from NIR-II-responsive gold nanobipyramids (GNBs) combined with curcumin (Cur) via hydrophobic-hydrophobic interactions and hydrogen bonds. On the basis of drug discovery and network pharmacology, we found that Cur has impressive anti-HSP90 capability and analyzed its therapeutic mechanism against NSCLC. Under the irradiation of NIR-II light, the obtained GNBs-Cur blocked the expression of HPS90 and inhibited related antiapoptotic pathways, thus enhancing the mild PTT of GNBs under 1064 nm laser irradiation. Meanwhile, Cur served as chemotherapeutic agents to induce apoptosis in tumor cells. In vivo photoacoustic imaging-guided, GNBs-Cur achieved effective tumor elimination through mild-photothermal chemotherapy without systemic toxicity. Overall, this work provides a new therapeutic modality paradigm for potential NSCLC treatment on the basis of synergistic therapies.
研究领域:
癌症治疗
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纳米技术
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药理学
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生物信息学
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医学成像
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Ping-fu Huang,Miaomiao Ma,Hao Wu,Wen-min Niu,Lu-lu Liu,Jia-bing Tong
Purpose Rheumatoid arthritis (RA) is an autoimmune disease with systemic inflammatory. Ibuprofen (IBF) and curcumin (CUR) were the commonly therapeutic ingredients for RA treatment and the combination administration possessed the ideal efficacy, however, the low solubility and lack of targeting produced the significant obstacles for the treatment. Methods In this study, the IBF prodrug decorated with the CD44 receptors and ROS-sensitive was prepared and encapsulated with the CUR named CUR@HA-TK-IBF were designed, the characterization of CUR@HA-TK-IBF were performed in vitro and the efficacity effect were evaluated using collagen induced arthritis (CIA) model. Results The obtained product CUR@HA-TK-IBF exhibited the diameter of 137.3 ± 4.5 nm, and the morphology of the nanoparticles showed the sphericity via the TEM. In vitro release results indicated that the IBF and CUR could slowly release in the normal environment and quickly release at the H 2 O 2 environment. Furthermore, the combination of CUR and IBF could significantly decrease the expression of the proinflammatory factors and the concentration of ROS and COX-2 in vitro . The animal experiment indicated that the CUR@HA-TK-IBF could alleviate the foot tumefaction and decrease the expression of proinflammatory factors in the RA model mice. Conclusion The CUR@HA-TK-IBF developed the new approach for co-deliver the IBF and CUR, which provided a new therapeutic strategy for the treatment of RA.
研究领域:
药学
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免疫学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF ONCOLOGY
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2024
·Vol. 64
·期 4
·1-12
·
IF 4.5
Sujuan Li,Sen Wang,Anping Zhang,Lixia Luo,Jie Song,Guoli Wei,Zhijun Fang
The immunogenic cell death (ICD) has aroused great interest in cancer immunotherapy. Doxorubicin (DOX), which can induce ICD, is a widely used chemotherapeutic drug in liver cancer. However, DOX‑induced ICD is not potent enough to initiate a satisfactory immune response. Cucurbitacin IIa (CUIIa), a tetracyclic triterpene, is a biologically active compound present in the Cucurbitaceae family. The present study assessed the effects of the combination of DOX and CUIIa on the viability, colony formation, apoptosis and cell cycle of HepG2 cells. In vivo anticancer effect was performed in mice bearing H22 tumor xenografts. The hallmark expression of ICD was tested using immunofluorescence and an ATP assay kit. The immune microenvironment was analyzed using flow cytometry. The combination of CUIIa and DOX displayed potent apoptosis inducing, cell cycle arresting and in vivo anticancer effects, along with attenuated cardiotoxicity in H22 mice. The combination of DOX and CUIIa also facilitated ICD as manifested by elevated high‑mobility group box 1, calreticulin and ATP secretion. This combination provoked a stronger immune response in H22 mice, including dendritic cell activation, increment of cytotoxic T cells and T helper 1 cells. Moreover, the proportion of immunosuppressive cells including myeloid‑derived suppressor cells, T regulatory cells and M2‑polarized macrophages, decreased. These data suggested that CUIIa is a promising combination partner with DOX for liver cancer treatment, probably via triggering ICD and remolding the immune microenvironment.
研究领域:
肿瘤学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2024
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IF 4.9
Ziwei Yan,Hui Zhang,Jinghao Chen,Qingqing Xu,Shuaipeng Feng,Qinfu Zhao,Siling Wang
Photothermal effect produced in photothermal therapy (PTT) can not only eradicate tumors but also allow the promotion of biological and chemical reactions in tumor tissues, leading to the potential of photothermal-enhanced anti-tumor therapy with desirable outcomes. Biodegradable polydopamine (PDA) nanoparticles exhibit remarkable photothermal conversion efficiency and stability, making them ideal photothermal agents (PTAs) to achieve photothermal-enhanced anti-tumor therapy. The high affinity of PDA to metal ions provides a broad application prospect for the development of multi-functional nanoplatforms to achieve cancer therapy with high efficacy and specificity. In this work, we fabricated Cu(II)-doped mesoporous PDA nanoparticles with polyethylene glycol (PEG) modified (CMP-P), which not only possessed higher photothermal conversion efficacy than mesoporous PDA nanoparticles , but also presented distinctive self-enhanced chemodynamic (CDT) performance. CMP-P mediated CDT was predicated on catalyzing the Fenton-like reaction to generate hydroxyl radicals (·OH). Impressively, CMP-P further triggered glutathione (GSH) depletion intracellular to prevent the consumption of ·OH, and the photothermal effect further improved ·OH generation. Meanwhile, CMP-P exhibited favorable degradability, the process of which was elaborated intuitively by transmission electron microscope (TEM). CMP-P was then employed for doxorubicin (DOX) loading, and enabled the enhanced DOX release in-situ under the stimulation of photothermal effect and tumor micro-environment (TME). The lower IC 50 value of DOX/CMP-P (1.68 μg/mL) than the signal therapy suggested the superior synergistic effect of DOX/CMP-P. Meanwhile, in vivo experiments also revealed the considerably improved anti-tumor efficacy of synergistic therapy mediated by DOX/CMP-P.
研究领域:
生物医学工程
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纳米医学
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癌症治疗
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材料科学
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产品关联
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Guanghao Li,Yujun Bao,Hui Zhang,Jingchun Wang,Xiaodan Wu,Rui Yan,Zhiqiang Wang,Yingxue Jin
Tumor metastasis and recurrence are closely related to immune escape and hypoxia. Chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT) can induce immunogenic cell death (ICD), and their combination with immune checkpoint agents is a promising therapeutic strategy. Iron based nanomaterials have received more and more attention, but their low Fenton reaction efficiency has hindered their clinical application. In this study, Fe 3 O 4 -carbon dots complex (Fe 3 O 4 -CDs) was synthesized, which was modified with ferrocenedicarboxylic acid by amide bond, and crosslinked into Fe 3 O 4 -CDs@Fc nano complex. The CDs catalyzed the Fenton reaction activity of Fe 3 O 4 by helping to improve the electron transfer efficiency, extended the reaction pH condition to 7.4. The Fe 3 O 4 -CDs@Fc exhibit exceptional optical activity, achieving a thermal conversion efficiency of 56.43 % under 808 nm light and a photosensitive single-line state oxygen quantum yield of 33 % under 660 nm light. Fe 3 O 4 -CDs@Fc improved intracellular oxygen level and inhibited hypoxia-inducing factor (HIF-1 α ) by in-situ oxygen production based on Fenton reaction. The multimodal combination of Fe 3 O 4 -CDs@Fc (CDT/PDT/PTT) strongly induced immune cell death (ICD). The expression of immune-related protein and HIF-1 α was investigated by immunofluorescence method. In vivo, Fe 3 O 4 -CDs@Fc combined with immune checkpoint blocker (antibody PD-L1, αPD-L1) effectively ablated primary tumors and inhibited distal tumor growth. Fe 3 O 4 -CDs@Fc is a promising immune-antitumor drug.
研究领域:
纳米技术
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癌症治疗
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生物医学工程
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免疫疗法
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 5
·1181
·
IF 4.2
Minghe Wang,Zhouyuji Liao,Dongting Zhangsun,Yong Wu,Sulan Luo
Antimicrobial peptides (AMPs), acknowledged as host defense peptides, constitute a category of predominant cationic peptides prevalent in diverse life forms. This study explored the antibacterial activity of α-conotoxin RgIA, and to enhance its stability and efficacy, D-amino acid substitution was employed, resulting in the synthesis of nine RgIA mutant analogs. Results revealed that several modified RgIA mutants displayed inhibitory efficacy against various pathogenic bacteria and fungi, includingCandida tropicalisandEscherichia coli. Mechanistic investigations elucidated that these polypeptides achieved antibacterial effects through the disruption of bacterial cell membranes. The study further assessed the designed peptides’ hemolytic activity, cytotoxicity, and safety. Mutants with antibacterial activity exhibited lower hemolytic activity and cytotoxicity, with Pep 8 demonstrating favorable safety in mice. RgIA mutants incorporating D-amino acids exhibited notable stability and adaptability, sustaining antibacterial properties across diverse environmental conditions. This research underscores the potential of the peptide to advance innovative oral antibiotics, offering a novel approach to address bacterial infections.
研究领域:
药理学
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微生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Minghui Li,Jiabi Wu,Tao Yang,Yuhang Zhao,Ping Ren,Lingling Chang,Pilong Shi,Jing Yang,Yuhang Liu,Xiaolei Li,Peng Wang,Yonggang Cao
Background Cardiac microvascular damage is substantially related with the onset of myocardial ischaemia-reperfusion (IR) injury. Reportedly, allicin (AL) effectively protects the cardiac microvascular system from IR injury. However, the unsatisfactory therapeutic efficacy of current drugs and insufficient drug delivery to the damaged heart are major concerns. Here, inspired by the natural interaction between neutrophils and inflamed cardiac microvascular endothelial cells (CMECs), a neutrophil membrane-camouflaged nanoparticle for non-invasive active-targeting therapy for IR injury by improving drug delivery to the injured heart is constructed.Methods In this study, we engineered mesoporous silica nanoparticles (MSNs) coated with a neutrophil membrane to act as a drug delivery system, encapsulating AL. The potential of the nanoparticles (named AL@MSNs@NM) for specific targeting of infarcted myocardium was assessed using small animal vivo imaging system. The cardiac function of AL@MSNs@NM after treatment was evaluated by Animal Ultrasound Imaging system, HE staining, and Laser Speckle Imaging System. The therapeutic mechanism was analyzed by ELISA kits, immunofluorescence, and PCR.Results We discovered that AL@MSNs@NM significantly improves cardiac function index, reduced infarct size and fibrosis, increased vascular perfusion in ischemic areas, and also promoted the function of CMECs, including migration, tube formation, shear stress adaptation, and nitric oxide production. Further research revealed that AL@MSNs@NM have cardio-protective functions in IR rats by inhibiting CMEC ferroptosis and increasing platelet endothelial cell adhesion molecule-1 (PECAM-1) expression.Conclusion Our results indicated that AL@MSNs@NM significantly reversed CMEC ferroptosis and increased PECAM-1 expression, enhanced cardiac function, and reduced myocardial infarction size. Therefore, this strategy demonstrates that engineered biomimetic nanotechnology effectively delivers AL for targeted therapy of myocardial infarction.
研究领域:
心血管科学
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纳米技术
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL BIOCHEMISTRY AND FUNCTION
·
2024
·Vol. 42
·期 8
·e70015
·
IF 2.8
Yang Yu,Tianchan Zhang,Xin Li,Tianyang Yu,Fanci Meng,Yifeng Luan,Huifang Cong,Xiuhong Wu
Perimenopausal syndrome is a significant issue that disturbs women's metabolism, mood and quality of life. Apigenin (4′,5,7-trihydroxyflavone) is a natural flavonoid that exhibits antioxidant, anti-inflammatory and anticancer effects. The present study aims to investigate the effect of apigenin on perimenopausal syndrome by combining bioinformatics analysis with in vivo experiments. The mouse model with perimenopausal syndrome was established using 4-vinylcyclohexene diepoxide (VCD) treatment. Apigenin alleviated VCD-induced disorder of estrous cycle and shrinkage of ovarian tissue. The reduction of anti-Muller hormone and the increase of follicle stimulation hormone and luteinizing hormone triggered by VCD were reversed by apigenin in a dose-dependent manner. Apigenin suppressed the VCD-induced decrease of primordial, primary, secondary and antral follicle number in ovarian tissue. Oxidative stress in ovarian tissue was activated by VCD treatment through increasing the reactive oxygen species production. High concentration of apigenin significantly reversed the alteration induced by VCD. Apigenin alleviated VCD-induced cell apoptosis through regulating Bax, Bcl-2, cleaved PARP1 and caspase-3. Furthermore, the phosphorylation of AKT and FOXO3a was inhibited by VCD and activated by apigenin in a dose-dependent manner. Collectively, apigenin effectively mitigates the ovarian dysfunction through suppressing oxidative stress and apoptosis via the AKT/FOXO3a signaling pathway. Summary Perimenopausal syndrome characterized by endocrine disorders, and hormone disorders has caused physical and mental damage to the majority of women. This study aims to explore a safe and effective method for perimenopausal syndrome treatment. Apigenin is a natural flavonoid that has protective effects on ovary, while the effect and mechanism of apigenin on perimenopausal syndrome is still unclear. This study's principal finding was that apigenin alleviated the estrous cycle disorder, follicle development inhibition and hormone level disorder in model with perimenopausal syndrome. Additionally, apigenin suppressed oxidative stress and apoptosis via activating the AKT/FOXO3a signaling pathway in the ovarian tissue of perimenopausal mice model. This work provides an effective approach for the remission and treatment of perimenopausal syndrome.
研究领域:
药理学
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内分泌学
·
妇科学
·
生物信息学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomedical Materials
·
2024
·
IF 3.9
Xin Hao,Ting Du,Feng Yang,Yilan Wang,Huatao He,Menghan Yang,Meiying Hong,Guanxiong Wang,Deqing Huang,Yaolei Wang
Recently, in vitro models of intestinal mucosa have become important tools for drug screening and studying the physiology and pathology of the intestine. These models enable the examination of cellular behavior in diseased states or in reaction to alterations in the microenvironment, potentially serving as alternatives to animal models. One of the major challenges in constructing physiologically relevant in vitro models of intestinal mucosa is the creation of three-dimensional (3D) microstructures that accurately mimic the integration of intestinal epithelium and vascularized stroma. Here, core-shell alginate (Alg) microspheres were generated to create the compartmentalized extracellular matrix (ECM) microenvironment needed to simulate the epithelial and vascularized stromal compartments of the intestinal mucosa. We demonstrated that NIH-3T3 and human umbilical vein endothelial cells (HUVECs) embedded in the core of the microspheres can proliferate and develop a vascular network, while human colorectal adenocarcinoma cells (Caco-2) can form an epithelial monolayer in the shell. Compared to Caco-2 monolayer encapsulated within the shell, the presence of the vascularized stroma enhances their proliferation and functionality. As such, our core-shell Alg microspheres provide a valuable method for generating in vitro models of vascularized intestinal mucosa with epithelial and vascularized stroma arranged in a spatially relevant manner and demonstrating near-physiological functionality.
研究领域:
生物医学工程
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组织工程
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细胞生物学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH BULLETIN
·
2025
·
IF 3.7
Qiyu Yang,Chunyan Wang,Jingwei Cao,Zhanbin Tang,Shurong Duan
Intracerebral hemorrhage (ICH) is associated with the highest rates of mortality and residual disability. To date, effective treatments to delay or prevent ICH are still lacking. Multiple forms of neuronal cell death have been discovered following ICH, including apoptosis, necrosis, autophagy, and ferroptosis. Aldo-keto reductase family 1 member C1 (AKR1C1) has been identified to act as a protective factor in ferroptosis. However, whether AKR1C1 was involved in the development of ICH was unknown. In this study, the left cerebral striatum of the Sprague-Dawley rat was injected with collagenase type IV to induce an in vivo model. Primary rat cortical neurons treated with oxygen hemoglobin (OxyHb) were applied to as an in vitro model. AKR1C1 was found to be downregulated and immunoreactivity colocalized with NeuN-positive neurons in the perihematomal region. Rats injected with lentiviral particles overexpressing AKR1C1 showed the reduction of cerebral hematoma and the remission of blood-brain barrier disruption. Moreover, AKR1C1 upregulation repressed cell apoptosis and ferroptosis induced by ICH through downregulating the expression of pro-apoptotic factors, inhibiting iron accumulation and lipid peroxidation, along with increasing the expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). The results of in vitro assays were consistent with results from the in vivo . Mechanistically, P53 overexpression augmented the cellular damage in OxyHb-stimulated neurons when AKR1C1 was overexpressed. Taken together, AKR1C1 improves ICH injury by inhibiting neuronal cell death via negatively regulating P53 expression and affecting the SLC7A11/GPX4 pathway.
研究领域:
神经科学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RESPIRATORY RESEARCH
·
2024
·Vol. 25
·期 1
·1-13
·
IF 4.7
Zhu Li,Wu Zhuhua,Liu Yingli,Ming Yue,Xie Pei,Jiang Miao,Qi Yong
Background Obesity is the main risk factor leading to the development of various respiratory diseases, such as asthma and pulmonary hypertension. Pulmonary microvascular endothelial cells (PMVECs) play a significant role in the development of lung diseases. Aconitate decarboxylase 1 (Acod1) mediates the production of itaconate, and Acod1/itaconate axis has been reported to play a protective role in multiple diseases. However, the roles of Acod1/itaconate axis in the PMVECs of obese mice are still unclear.Methods mRNA-seq was performed to identify the differentially expressed genes (DEGs) between high-fat diet (HFD)-induced PMVECs and chow-fed PMVECs in mice (|log2 fold change| ≥ 1, p ≤ 0.05). Free fatty acid (FFA) was used to induce cell injury, inflammation and mitochondrial oxidative stress in mouse PMVECs after transfection with the Acod1 overexpressed plasmid or 4-Octyl Itaconate (4-OI) administration. In addition, we investigated whether the nuclear factor erythroid 2-like 2 (Nrf2) pathway was involved in the effects of Acod1/itaconate in FFA-induced PMVECs.Results Down-regulated Acod1 was identified in HFD mouse PMVECs by mRNA-seq. Acod1 expression was also reduced in FFA-treated PMVECs. Acod1 overexpression inhibited cell injury, inflammation and mitochondrial oxidative stress induced by FFA in mouse PMVECs. 4-OI administration showed the consistent results in FFA-treated mouse PMVECs. Moreover, silencing Nrf2 reversed the effects of Acod1 overexpression and 4-OI administration in FFA-treated PMVECs, indicating that Nrf2 activation was required for the protective effects of Acod1/itaconate.Conclusion Our results demonstrated that Acod1/Itaconate axis might protect mouse PMVECs from FFA-induced injury, inflammation and mitochondrial oxidative stress via activating Nrf2 pathway. It was meaningful for the treatment of obesity-caused pulmonary microvascular endotheliopathy.
研究领域:
呼吸系统疾病
·
分子生物学
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细胞生物学
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内分泌学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）