JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Qixiong Zhang,Shanshan Li,Jiandong Ren,Xia He,Houkui Shi,Fuzhong Zhang,Hui Li,Rongsheng Tong
Due to its complexity, diversity and heterogeneity, melanoma is a kind of malignant tumor. It has been proved that the enhancement of anti-tumor immune response such as immunogenic cell death (ICD) is an important therapeutic strategy. In previous studies, we confirmed that dermatan sulfate (DS) from skin tissue could specifically homing to melanoma B16F10 cells. In this study, we propose a nanoinducer (DOX/ADS NP) based on a functional DS for melanoma. This nanosystem is composed of DS as framework, aromatic thioketal derivative (ATK) as functional grafting unit and doxorubicin (DOX) designed as an ICD inducer. Through the intermolecular interaction between DOX and ATK, DOX/ADS NP with specific-homing, high-loading and ROS-triggering release was obtained via self-assemble. Compared with free DOX and non-functionalized nanomedicine , DOX/ADS NP could release DOX into B16F10 cells better, and strongly induce the translocation of calreticulin (CRT) to the cell membrane . CRT is a marker of ICD, also as a “eat me” signal to stimulate the maturation and antigen presentation of dendritic cells. Therefore, a series of subsequent immune responses were activated: maturation of dendritic cells, T cells proliferation, increased tumor-infiltrating CTLs and the ratio of CTLs to Tregs, and up-regulated cytotoxic cytokine expression. In conclusion, DOX/ADS NP promoted ICD-associated immune response through more specific targeting effect and sensitive responsive DOX release, achieving better inhibitory effect on melanoma than free DOX and other nanoformulation. This biomimetic ICD nanoinducer based on DS is expected to provide new strategies and references for the treatment of melanoma.
研究领域:
肿瘤学
·
免疫疗法
·
纳米技术
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small Methods
·
2024
·
IF 10.7
Weitong Hu,Shuhan Shi,Yihua Xu,Yunting Zhang,Jingyi Hu,Qiong Bian,Xiaolu Ma,Yuxian Ye,Shengfei Yang,Xiaoxia Sheng,Guang Liang,Tianyuan Zhang,Haibin Wu,Jianqing Gao
Androgenetic alopecia (AGA) is a prevalent issue affecting the physical and mental health of individuals but with fewer current treatments. Platinum nanozymes (PtNZs) are known for their excellent ability to reduce and modulate the high oxidative stress environment in AGA pathology. And microneedles are used to overcome the skin barrier due to the poor permeability of PtNZs. Herein, dissolving microneedles loaded with PtNZs (Pt-MNs) are designed and successfully induced hair regeneration in the AGA model. Pt-MNs possessed adequate mechanical strength to breach the skin barrier for effective PtNZs delivery. In vivo, PtNZs first reduced reactive oxygen species (ROS) to oxygen, which recovered the AGA pathological environment. And the oxygen then increased oxidative phosphorylation, promoting the differentiation of hair follicle stem cells to achieve hair regeneration. The group treated with Pt-MNs with a dosing frequency of once every three days achieved faster hair growth than the daily application of the positive drug minoxidil. Further safety experiments showed that the application of Pt-MNs locally opened temporary and recoverable skin channels, with no retention of Pt in major organs, indicating high safety. In conclusion, this study indicated the potential of Pt-MNs as an effective method for treating AGA.
研究领域:
药学
·
纳米技术
·
皮肤科
·
生物医学工程
·
干细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2024
·
IF 5.4
Wajiha Ahmed,Shifen Li,Min Liang,Yongyuan Kang,Xiaoqing Liu,Changyou Gao
Elevated levels of ROS, bacterial infection, inflammation, and improper regeneration are the factors that need to be addressed simultaneously for achieving effective wound healing without scar formation. This study focuses on the fabrication of electrospun ROS-responsive selenium-containing polyurethane nanofibers incorporating deferoxamine mesylate (Def), indomethacin (Indo), and gold nanorods (AuNRs) as proangiogenesis, anti-inflammatory, and antibacterial agents for synchronized delivery to a full-thickness wound in vivo. The structure of the fabricated nanofibers was analyzed by various techniques. Toxicity was checked by CCK-8 and hemolytic assays. The efficiency of wound healing in vitro was verified by a transwell assay and cell scratch assay. The wound healing efficiency of the nanofibers was assayed in full-thickness wounds in a rat model. The multifunctional nanofibers had a porous structure, enhanced antioxidation, antibacterial activity, and promoted wound healing. They eradicated TNF-α and IL-6, increased IL-10 expression, and revealed the angiogenic potential by increased expression of HIF-1α, VEGF, and CD31.
研究领域:
材料科学
·
纳米技术
·
生物医学工程
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF SUPERCRITICAL FLUIDS
·
2022
·
IF 4.514
Jin-Zhou Rui,Hu-Hong Peng,Yi-Xin Guan,Shan-Jing Yao
Drug-loaded hydrogels with wound environment stimuli-responsive property can significantly promote wound healing and are widely applied in dressings. Two natural polymers , i.e. sodium alginate and sodium hyaluronate , were modified by 3-aminophenylboric acid and then cross-linked with polyvinyl alcohol to prepare ROS responsive hydrogels. Doxycycline hydrochloride was loaded onto hydrogels using supercritical solvent impregnation (SSI) technology, and the effects of immersion time, pressure and temperature on drug loading capacity (DLC) were investigated. DLC firstly increased and then decreased with the elevation of supercritical CO 2 pressure, and maximum value was up to 11 mg/g at 15 MPa and 50 °C. In the in vitro drug release study, doxycycline hydrochloride was controllably released from hydrogels for 10 h via the sensitivity of boronate ester bonds to ROS. This work expands the application of SSI in wound dressing, which provides a new approach for the design of composite hydrogel formulations with uniform drug distribution.
研究领域:
材料科学
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2023
·
IF 14
Fengying Shao,Jianyu Han,Zhaoyan Tian,Zhi Wang,Songqin Liu,Yafeng Wu
Taking advantage of endogenous Ca 2+ to upregulate intramitochondrial Ca 2+ level has become a powerful mean for mitochondrial dysfunction-mediated tumor therapy. However, the Ca 2+ entered into mitochondria is limited ascribing to the uncontrollability and non-selectivity of endogenous Ca 2+ transport. It remains a great challenge to make the maximum use of endogenous Ca 2+ to ensure sufficient Ca 2+ overloading in mitochondria. Herein, we smartly fabricate an intracellular Ca 2+ directional transport channel to selectively transport endogenous Ca 2+ from endoplasmic reticulum (ER) to mitochondria based on cascade release nanoplatform ABT-199@liposomes/doxorubicin@Fe III -tannic acid (ABT@Lip/DOX@Fe-TA). In tumor acidic microenvironment , Fe 3+ ions are firstly released and reduced by tannic acid (TA) to Fe 2+ for ROS generation. Subsequently, under the NIR light irradiation, the released ABT-199 molecules combine with ROS contribute to the formation of IP3R-Grp75-VDAC1 channel between ER and mitochondria, thus Ca 2+ ions are directionally delivered and intramitochondrial Ca 2+ level is significantly upregulated. The synergetic ROS generation and mitochondrial Ca 2+ overloading effectively intensifies mitochondrial dysfunction, thereby achieving efficient tumor inhibition. This work presents a new insight and promising avenue for endogenous Ca 2+ -involved tumor therapies.
研究领域:
肿瘤学
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2021
·Vol. 11
·期 4
·2101855
·
IF 9.933
Jieqi Xie,Yuejun Yao,Shuqin Wang,Linge Fan,Jie Ding,Yun Gao,Shifen Li,Liyin Shen,Yang Zhu,Changyou Gao
Excessive reactive oxygen species (ROS) generated after myocardial infarction (MI) result in the oxidative injury in myocardium. Implantation of antioxidant biomaterials, without the use of any type of drugs, is very appealing for clinical translation, leading to the great demand of novel biomaterials with high efficiency of ROS elimination. In this study, a segmented polyurethane (PFTU) with a high density of ROS-scavenging backbone units is synthesized by the reaction of poly(thioketal) dithiol (PTK) and poly(propylene fumarate) diol (PPF) (soft segments), thioketal diamine (chain extender), and 1,6-hexamethylene diisocyanate (HDI). Its chemical structure is verified by gel permeation chromatography (GPC), 1 H nuclear magnetic resonance ( 1 H NMR) spectroscopy, and Fourier transform infrared (FTIR) spectroscopy. The electrospun composite PFTU/gelatin (PFTU/Gt) fibrous patches show good antioxidation capacity and ROS-responsive degradation in vitro. Implantation of the PFTU/gelatin patches on the heart tissue surface in MI rats consistently decreases the ROS level, membrane peroxidation, and cell apoptosis at the earlier stage, which are not observed in the non-ROS-responsive polyurethane patch. Inflammation and fibrosis are also reduced in the PFTU/gelatin-treated hearts, resulting in the reduced left ventricular remodeling and better cardiac functions postimplantation for 28 d.
研究领域:
材料科学
·
心脏病学
·
生物材料工程
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
CELLULAR AND MOLECULAR NEUROBIOLOGY
·
2016
·Vol. 36
·期 8
·1365-1375
·
IF 2.328
Lin Xuemei,Wu Songdi,Wang Qing,Shi Yaling,Liu Guozheng,Zhi Jin,Wang Fang
Neuronal oxidative stress (OS) injury has been proven to be associated with many neurodegenerative diseases, and thus, antioxidation treatment is an effective method for treating these diseases. Saikosaponin-D (SSD) is a sapogenin extracted from Bupleurum falcatum and has been shown to have many pharmacological activities. The main purpose of this study was to investigate whether and how SSD protects PC12 cells from H 2 O 2 -induced apoptosis. The non-toxic level of SSD significantly mitigated the H 2 O 2 -induced decrease in cell viability, reduced the apoptosis rate, improved the nuclear morphology, and reduced caspase-3 activation and poly ADP-ribose polymerase (PARP) cleavage. Additionally, exogenous H 2 O 2 -induced apoptosis by damaging the intracellular antioxidation system. SSD significantly slowed the H 2 O 2 -induced release of malonic dialdehyde (MDA) and lactate dehydrogenase and increased the activity of superoxide dismutase (SOD) and the total antioxidant capacity, thereby reducing apoptosis. More importantly, SSD effectively blocked H 2 O 2 -induced phosphorylation of extracellular-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38MAPK), and specific inhibitors of ERK, JNK, and p38-reduced OS injury and apoptosis, suggesting that SSD reduces OS injury and apoptosis via MAPK signalling pathways. Finally, we confirmed that SSD significantly reduced H 2 O 2 -induced reactive oxygen species (ROS) accumulation, and the ROS inhibitor blocked the apoptosis caused by MAPK activation and cellular oxidative damage. In short, our study confirmed that SSD reduces H 2 O 2 -induced PC12 cell apoptosis by removing ROS and blocking MAPK-dependent oxidative damage.
研究领域:
神经科学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2023
·
IF 15.1
Huiyun Li,Yusong Yuan,Lingpu Zhang,Chun Xu,Hailin Xu,Zhiwei Chen
Osteoarthritis (OA) is a chronic joint disease characterized by synovitis and joint cartilage destruction. The severity of OA is highly associated with the imbalance between M1 and M2 synovial macrophages. In this study, a novel strategy is designed to modulate macrophage polarization by reducing intracellular reactive oxygen species (ROS) levels and regulating mitochondrial function. A ROS-responsive polymer is synthesized to self-assemble with astaxanthin and autophagy activator rapamycin to form nanoparticles (NP@Poly RHAPM ). In vitro experiments show that NP@Poly RHAPM significantly reduced intracellular ROS levels. Furthermore, NP@Poly RHAPM restored mitochondrial membrane potential, increased glutathione (GSH) levels, and promoted intracellular autophagy, hence successfully repolarizing M1 macrophages into the M2 phenotype. This repolarization enhanced chondrocyte proliferation and vitality while inhibiting apoptosis. In vivo experiments utilizing an anterior cruciate ligament transection (ACLT)-induced OA mouse model revealed the anti-inflammatory and cartilage-protective effects of NP@Poly RHAPM , effectively mitigating OA progression. Consequently, the findings suggest that intra-articular delivery of ROS-responsive nanocarrier systems holds significant promise as a potential and effective therapeutic strategy for OA treatment.
研究领域:
药理学
·
生物医学工程
·
骨科
·
免疫学
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Nan Hu,Meng Sun,Nan Lv,Yangyang Gao,Xiaohong Fu,Dayi Xing,Xiang Guo,Shaodong Zhai,Ruiping Zhang
Myocardial infarction (MI) is the leading cause of death worldwide. The most effective way to treat myocardial infarction is to rescue ischemic cardiomyocytes. After an ischemic event, the overproduction of reactive oxygen species (ROS) is a key driver of myocardial injury. The produced ROS affects mitochondrial function and induces apoptosis in cardiomyocytes. This was accomplished by constructing platelet-membrane-encapsulated ROS-responsive drug-releasing nanoparticles (PMN@NIC-MalNPs) to deliver malonate and niclosamide (NIC). The results revealed that PMN@NIC-MalNPs degraded and released malonate and niclosamide in a high-level ROS microenvironment, effectively reducing the oxidative stress and apoptosis rate. By enhancing basal mitochondrial oxygen consumption rate (OCR), adenosine triphosphate (ATP) production, and spare respiratory capacity (SRC) in vitro, reduced the oxidative stress levels and restored mitochondrial function. In vivo studies revealed that the PMN@NIC-MalNPs improved cardiac dysfunction, inhibited succinate dehydrogenase (SDH) activity, increased ATP production, and reduced the myocardial infarct size in myocardial infarction model mice. Further, transcriptome analysis and Western blot revealed that PMN@NIC-MalNPs prevented apoptosis by activating the expressions of the signal transducer and activator of transcription 3 (STAT3) and Bcl-2, and inhibiting the expression of Bax. Thus, this study provides a novel therapeutic solution for treating myocardial infarction and predicting the viability of an antioxidant and antiapoptotic therapeutic solution in the treatment of myocardial injury.
研究领域:
心脏病学
·
药学
·
纳米技术
·
分子生物学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Bingqing Zhang,Qiang Li,Qinglin Xu,Baochao Li,Heng Dong,Yongbin Mou
Background Inflammatory bowel disease (IBD) is closely related to higher intracellular oxidative stress. Therefore, developing a novel method to scavenge the harmful reactive oxygen species (ROS) and alleviate colon inflammation to treat IBD is a promising strategy.Methods CeO2@PDA-PEG (CeO2@PP) were synthesized by modifying ceria (CeO2) nanorods with polydopamine (PDA) and polyethylene glycol (PEG). The ROS scavenging ability of CeO2@PP was detected by using flow cytometry and confocal laser scanning microscope (CLSM). The anti-inflammatory ability of CeO2@PP was determined in vitro by treating lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The biocompatibility of CeO2@PP was evaluated in vivo and in vitro. Moreover, the therapeutic effects of CeO2@PP in vivo were estimated in a dextran sulfate sodium salt (DSS)-induced colitis mouse model.Results Physicochemical property results demonstrated that PDA and PEG modification endowed CeO2 nanorods with excellent dispersibility and colloidal stability. CeO2@PP maintained superior enzyme-like activity, including superoxide dismutase (SOD) and catalase (CAT), indicating antioxidant ability. Moreover, in vitro results showed that CeO2@PP with PDA promotes LPS-induced RAW 264.7 macrophages into M2-type polarization. In addition, in vitro and in vivo results showed that CeO2@PP have great biocompatibility and biosafety. Animal experiments have shown that CeO2@PP have excellent anti-inflammatory effects against DSS-induced colitis and effectively alleviated intestinal mucosal injury.Conclusion The nanoplatform CeO2@PP possessed excellent antioxidant and anti-inflammatory properties for scavenging ROS and modulating macrophage polarization, which is beneficial for efficient colitis therapy.
研究领域:
纳米技术
·
药理学
·
免疫学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Plants-Basel
·
2025
·Vol. 14
·期 1
·120
·
IF 4.1
Fangjie Li,Chen Yang,Maoye Li,Su Liu,Kuo Xu,Xianjun Fu
Valsa mali(V. mali) is a necrotrophic fungus responsible for apple Valsa canker, which significantly diminishes apple production yields and quality in China. Our serendipitous findings revealed that genistein significantly inhibits the mycelial growth ofV. mali, with an inhibition rate reaching 42.36 ± 3.22% at a concentration of 10 µg/mL. Scanning electron microscopy analysis revealed that genistein caused significant changes in the structure ofV. mali, including mycelial contraction, distortion, deformity, collapse, and irregular protrusions. Transmission electron microscopy analysis revealed leakage of cellular contents, blurred cell walls, ruptured membranes, and organelle abnormalities. Genistein has been shown to increase reactive oxygen species levels inV. malimycelia, as demonstrated by 2′,7′-dichlorofluorescin diacetate staining. This increase was associated with a decrease in superoxide dismutase activity alongside increases in catalase and peroxidase activities. These changes collectively disrupted the oxidative equilibrium, leading to the induction of oxidative stress. The transcriptomic analysis revealed 13 genes enriched in this process, linked to unsaturated fatty acid biosynthesis (three downregulated DEGs), saturated fatty acid biosynthesis (three upregulated and six downregulated DEGs), and fatty acid metabolism (four upregulated and nine downregulated DEGs). Additionally, the downregulated DEGs VMIG_07417 and VMIG_08675, which are linked to ergosterol biosynthesis, indicate possible changes in membrane composition. In conjunction with the qRT-PCR results, it is hypothesized that genistein exerts an antifungal effect onV. malithrough ROS-mediated lipid peroxidation. This finding has the potential to contribute to the development of novel biological control agents for industrial crops.
研究领域:
植物病理学
·
真菌学
·
植物病原学
·
生物技术
·
农业科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2021
·
IF 4.749
Yahong Liu,Longfei Miao,Yuying Guo,Renbin Yuan,Xuejiao Li,Xinxin Wang,Xiaona Lin,Hongqi Tian
Protecting the body from radiation damage is a huge medical challenge. Amifostine and curcumin are both effective radioprotectants, but their use has been greatly restricted due to various reasons including low bioavailability. Nanoscale drug delivery systems of poly(ethylene glycol)–poly(ε-caprolactone) copolymers can improve the bioavailability of drugs due to excellent biocompatibility, biodegradability, and long circulation characteristics. In this study, a new reactive oxygen species-sensitive nanocarrier fabricated by linking curcumin and thioketal to poly(ethylene glycol)–poly(ε-caprolactone) polymer was used for delivery of WR-1065 (the active ingredient of amifostine). The content of curcumin in this polymer was about 7.6%, and the drug loading of WR-1065 was 44%. The WR-1065-loaded nanoparticles (NPs) had an average size of 128.6 nm and uniform spherical morphology. These WR-1065-loaded NPs reduced the metabolism of curcumin and WR-1065 in the gastrointestinal tract and could be well absorbed by cells and distributed to multiple organs. Compared with a single drug, oral administration of WR-1065-loaded NPs demonstrated obvious radioprotective effects on the hematopoietic system and prevented intestinal injury. The 30-day survival rate after half-lethal dose (7.2 Gy) of total body irradiation was 100%. In general, WR-1065-loaded NPs improved the oral bioavailability of WR-1065 and curcumin. This multifunctional nanocarrier provides a possibility for combination therapy in treating ionizing radiation damage.
研究领域:
药学
·
辐射生物学
·
纳米技术
·
药物递送系统
✓ 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）