International Journal of Nanomedicine
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2023
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IF 8
Tingting Song,Hong Wang,Yue Liu,Rongshan Cai,Dezhi Yang,Yongai Xiong
Background Ziyuglycoside I (ZgI), an active ingredient isolated from traditional Chinese medicine Sanguisorba officinalis L, has been demonstrated to increase the leucocytes and protect hematopoietic stem cells. However, the poor solubility and a short half-life of ZgI limit its bioavailability and efficacy. The D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) has been widely used to increase the solubility, improve the encapsulation rate, and extend the half-life of drugs.Methods Here, we formulated the TPGS-modified long-circulating liposomes loading ZgI with a sustained drug release and enhanced therapy for myelosuppression. ZgI-TPGS-liposomes were manufactured using a thin-film hydration technique, followed by characterizations of physicochemical properties, including the particle size, zeta potential, TEM, SEM, FTIR, XRD, stability, drug loading (DL), encapsulation efficiency (EE). The in vitro and in vivo delivery efficiency were further evaluated by cellular uptake, in vitro drug release and in vivo pharmacokinetics. Finally, therapeutic effect on myelosuppression was investigated.Results The ZgI-TPGS-liposomes had an particle size of 97.89 ± 1.42 nm and ZP of −28.65 ± 0.16 mV. It exhibited DL of 9.06 ± 0.76% and EE of 92.34 ± 3.83%, along with excellent storage stability, cellular uptake and sustained drug release to free ZgI and liposomes without TPGS. Additionally, the TPGS modified liposomes significantly enhanced the therapeutic effect of ZgI on CTX induced myelosuppression, which can be confirmed in the apoptosis inhibition and cell viability promotion of CTX injured HSPC-1 cells. Also, the mice in vivo pharmacodynamics demonstrated that TPGS liposomes promoted ZgI increasing the numbers of leucocytes and neutrophils in myelosuppression mice induced by CTX.Conclusion Our research suggest that TPGS-modified long-circulating liposomes loading ziyuglycoside I has potential application in myelosuppression therapy.
研究领域:
药剂学
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药理学
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纳米技术
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中药学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
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IF 8
Ayimukedisi Yalikong,Xu-Quan Li,Ping-Hong Zhou,Zhi-Peng Qi,Bing Li,Shi-Lun Cai,Yun-Shi Zhong
Background Colon cancer (CRC) was a malignant tumor and there were about 25% of patients with tumor metastasis at diagnosis stage. Chemotherapeutic agents for metastatic CRC patients were with great side effects and the clinical treatment results of advanced CRC were still not satisfactory. Human epidermal growth factor receptor 2 (HER2) is overexpressed in some CRC patients and is an effective target for CRC patient treatment. Anti-HER2 therapy had a beneficial role in the treatment of HER2-positive metastatic CRC with fewer side effects. CRC patients with BRAF mutations were resistant to HER2 antibodies treatment. Therefore, there was an urgent need to develop new therapeutic agents.Methods HER2 targeted nanoparticles (TPLNP) drug delivery system loading triptolide (TPL) were prepared and identified. The effects of TPLNP and free TPL on cell viability, targeting and cell cycle progression on HT29 (BRAF mutation) with HER2 overexpression, were evaluated by Cell Counting Kit-8 (CCK8), Fluorescence Activating Cell Sorter (FACS) and immunofluorescence methods, respectively. The anti-tumor efficacies of TPLNP were evaluated in subcutaneous xenograft model of colon cancer and the survival rate, tumor volume, liver and kidney indexes of tumor-bearing mice were measured.Results TPLNP was small in nanosize (73.4±5.2nm) with narrow size distribution (PDI=0.15±0.02) and favorable zeta potential (pH=9.6, zeta potential: −57.3±6.69mV; pH=7.0, zeta potential: −28.7±5.1mV; pH=5.6, zeta potential: −21.1±4.73mV). Comparing with free TPL treatment group, TPLNP developed stranger colon cancer-killing efficiency in a dose- and time-dependent manner detected with CCK8 method; achieved good in vitro colon cancer targeting detected with flow cytometry and immunofluorescence experiments; enhanced more HT29-HER2 apoptosis and induced more cell cycle arrested in G1-S phase detected with FACS in vitro. As for in vivo antitumor response, TPLNP remarkably inhibited the growth of colon cancer in the colon cancer xenograft model, significantly improved the survival rate and did not exhibit significant liver and kidney toxicity in contrast with free TPL in vivo.Conclusion TPLNP was effectively against colon cancer with HER2 overexpression and BRAF mutation in pre-clinical models. In summary, the TPLNP appeared to be a promising treatment option for CRC in clinical application based on improved efficacy and the favorable safety profile.
研究领域:
肿瘤学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2023
·Vol. 25
·期 5
·1-10
·
IF 2.7
Yujin Wang,Hua Jiang,Lijun Wang,Huiping Gan,Xinchun Xiao,Liangwu Huang,Wenxin Li,Zongrun Li
Functional constipation (FC), a common symptom that is primarily associated with intestinal motility dysfunction, is a common problem worldwide. Arctiin (Arc) is a lignan glycoside isolated from the Chinese herbal medicine Arctium lappa L., which is a health food in China. The present study aimed to evaluate the laxative effects of Arc against FC in mice. A model of FC induced by loperamide (5 mg/kg) was established in male Institute of Cancer Research (ICR) mice. Arc was administered at a dose of 100 mg/kg as a protective agent. The faecal status, intestinal motility and histological analyses were evaluated. Furthermore, the levels of gastrointestinal motility‑associated neurotransmitters, such as motilin (MTL), nitric oxide (NO), and brain‑derived neurotrophic factor (BDNF) and the protective effect of Arc on interstitial cells of Cajal (ICC) were assessed. Arc treatment reversed the loperamide‑induced reduction in faecal number and water content and the intestinal transit ratio in ICR mice. Histological analysis confirmed that Arc administration mitigated colonic injury. Moreover, Arc treatment increased levels of motilin and brain‑derived neurotrophic factor while decreasing nitric oxide levels and ICC injury in the colon of FC mice. Arc decreased inflammation induction and aquaporin expression levels. Owing to its pro‑intestinal motility property, Arc was shown to have a protective effect against FC and may thus serve as a promising therapeutic strategy for the management of FC.
研究领域:
药理学
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胃肠病学
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神经胃肠病学
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产品关联
DOI
PubMed
高影响因子
APL Bioengineering
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2023
·Vol. 7
·期 1
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IF 6
Wang Jun,Wu YanYan,Liu Kai,Yang Weitao,Zeng Weiwei,Gao Xiaolong,Liu ShiYuan,Zhang Bingbo
The development of a combination of chemo/photothermal therapy could overcome the limitations of single-modality therapy and enhance therapeutic efficacy. In this study, a pH/thermal dual-responsive multifunctional drug delivery system with dual-drug loading and enhanced chemo/photothermal therapy is developed based on polydopamine-coated mesoporous silica-gold nanorods (PDA-AuNRs@MSN). Nanoscale mesoporous silica-gold nanorods encapsulating doxorubicin (DOX) are designed as a core and then modified by polydopamine. The PDA shell not only conjugates with another anticancer bortezomib (Btz) to form pH-sensitive bond through boronic acid and catechol but also acts as a gatekeeper to control the release of doxorubicin and enhance the photothermal effect. Such a nanocarrier not only acts as a contrast agent for PA imaging but also serves as a therapeutic agent for enhanced chemo/photothermal therapy. The DOX and Btz could be released in an on-demand mode under near-infrared light irradiation and acid environment. The tumor size and location could be observed via PA imaging after intravenous injection into 4T1-bearing mice. Compared with AuNRs@MSN, PDA-AuNRs@MSN exhibit an increased near-infrared (NIR) absorption at 808 nm and an enhanced photothermal effect. The integrated D/B-PDA-AuNRs@MSN nanoparticles show higher cell apoptosis and enhanced tumor treatment efficacy in vitro and in vivo in comparison with single chemotherapy or photothermal therapy. Combined together, D/B-PDA-AuNRs@MSN show pH/thermal-responsive controlled-release and synergistic chemo/photothermal therapy for tumor.
研究领域:
生物医学工程
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肿瘤治疗
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纳米药物递送
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2021
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IF 13.273
Xiaoning Ren,Wenliang Liu,Houjian Zhou,Jianshuang Wei,Congpu Mu,Ying Wan,Xiaoquan Yang,Anmin Nie,Zhongyuan Liu,Xiangliang Yang,Zhiqiang Luo
Germanium phosphide (GeP), a new member of phosphorus-based 2D materials, is a semiconductor with indirect and narrowed band gap, which theoretically would have great potential to serve as near-infrared (NIR) photothermal agent (PTA) with high photothermal conversion efficiency (PTCE). However, the photothermal conversion performance and biomedical application of GeP-based nanocarriers has not been explored yet. Herein, we demonstrate the GeP nanosheets as high-performance PTA with PTCE of 68.6% in NIR region, which is much higher than many of other 2D PTA such as graphene, Mxenes, transition metal dichalcogenides, and black phosphorus (BP), and explore its application in multimodal cancer theranostics. Similar to BP nanosheets, the GeP nanosheets are biodegradable with excellent biocompatibility. With the merit of large specific surface area, the GeP nanosheets have high loading capacity (134 wt%) for anticancer drug Doxorubicin (DOX). The NH 2 -PEG-FA modified GeP-DOX hybrids show pH-responsive, heat-stimulative and sustained-drug-release performance as chemo-photothermal synergistic cancer therapy platform, and demonstrate remarkable tumor ablation ability both in vitro and in vivo . Meanwhile, multimodal imaging capability including photoacoustic imaging and photothermal imaging is also realized on basis of the excellent photothermal performance of GeP nanosheets. This study highlights the great promise of 2D GeP nanosheets as multifunctional platform for cancer theranostics application.
研究领域:
生物医学工程
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材料科学
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肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULES
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2021
·Vol. 27
·期 1
·128
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IF 4.412
Lixia Chen,Yang Zhang,Xinming Zhang,Ruijuan Lv,Rongtian Sheng,Ruimeng Sun,Ting Du,Yuhan Li,Yanfei Qi
Anticancer treatment is largely affected by the hypoxic tumor microenvironment (TME), which causes the resistance of the tumor to radiotherapy. Combining radiosensitizer compounds and O2self-enriched moieties is an emerging strategy in hypoxic-tumor treatments. Herein, we engineered GdW10@PDA-CAT (K3Na4H2GdW10O36·2H2O, GdW10, polydopamine, PDA, catalase, CAT) composites as a radiosensitizer for the TME-manipulated enhancement of radiotherapy. In the composites, Gd (Z = 64) and W (Z = 74), as the high Z elements, make X-ray gather in tumor cells, thereby enhancing DNA damage induced by radiation. CAT can convert H2O2to O2and H2O to enhance the X-ray effect under hypoxic TME. CAT and PDA modification enhances the biocompatibility of the composites. Our results showed that GdW10@PDA-CAT composites increased the efficiency of radiotherapy in HT29 cells in culture. This polyoxometalates and O2self-supplement composites provide a promising radiosensitizer for the radiotherapy field.Keywords:radiosensitizer;polyoxometalates;catalase;O2self-supplement;radiotherapy
研究领域:
癌症治疗
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放射肿瘤学
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材料科学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2022
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IF 8.025
Tianbao Wang,Jiahui Yang,Hongmei Kang,Liangke Zhang,Huan Chen
Photothermal therapy (PTT) is a potentially effective and non-invasive tumor therapy that has attracted the attention of many researchers. This study systematically investigated the formation of metal-polyphenol nanoparticles and their photothermal properties. A simple physical self-assembly method was used to embed hyaluronic acid (HA) into metal-polyphenol nanoparticles, and a novel type of HA-modified ferrous baicalein nanoparticle (HFBNP) was successfully prepared for the first time. Unlike most current methods that utilize positive and negative charge attraction or chemical bonding, the method proposed in this study is to embed HA into nanostructures to reduce the risk of HA shedding in the circulation, thereby improving the tumor targeting efficiency while avoiding the use of other chemical reagents. HFBNP had a suitable size distribution and good biosafety meanwhile efficiently converting near-infrared (NIR) laser energy into thermal energy. The active targeting capability mediated by HA significantly increased the uptake of nanoparticles by tumor cells, and HFBNP exhibited a strong growth inhibitory effect on tumor cells under NIR laser irradiation. With the combination of PTT and chemotherapy, HFBNP significantly inhibited tumor growth in tumor-bearing mice. In conclusion, the nanosystem prepared in this study provides a new strategy for tumor therapy.
研究领域:
生物医学工程
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肿瘤学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL ANIMALS
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2022
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IF 1.798
Qiushi LI,Xuying LIU,Ruixian XING,Rubo SUI
Stroke, a type of acute cerebrovascular disease, is a global disease with high mortality. Neuronal ischemia and hypoxia are closely related to occurrence and development of cognitive impairment. Transmembrane p24 trafficking protein 10 (TMED10) as a transmembrane protein involves in vesicle protein transport in the secretory pathways. However, the function and mechanism of TMED10 on ischemic stroke and cognitive impairments remain unclear. In current study, TMED10 was highly expressed in cerebral ischemic penumbra of middle cerebral artery occlusion (MCAO) mouse model. Downregulation of TMED10 suppressed cell survival and facilitated apoptosis in primary cortical neurons, which were grown under oxygen glucose deprivation/reoxygenation (OGD/R) condition. Upregulation of TMED10 protected neurons form apoptosis induced by OGD/R. Further research indicated that the decrease of TMED10 resulted in neuronal mitochondrial injury through increasing reactive oxygen species (ROS) production. Meanwhile, TMED10 reduction induced neuronal apoptosis and mitochondrial damage through activating the c-Jun N-terminal kinase (JNK) pathway. Moreover, the knockdown of TMED10 increased cerebral infarction area, aggravated neuronal injury and promoted neuronal apoptosis through activating the JNK pathway in the cerebral ischemic penumbra of MCAO mouse model. Additionally, Morris water maze test verified that the severity of cognitive impairment increased with the decline of TMED10. Collectively, this study reveals that TMED10 inhibits mitochondrial damage, and protects neurons from apoptosis in MCAO-induced ischemic stroke and cognitive impairment via blocking the JNK pathway.
研究领域:
神经科学
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分子生物学
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细胞生物学
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医学研究
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产品关联
DOI
PubMed
高影响因子
Frontiers in Oncology
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2022
·
IF 5.738
Kong Ji chuan,Li Yang,Ma Wang,Du Yu rong,Liu Lei,Qu Tian tian,Liu Shuo shuo,Wang Meng li,Dou Wei
As an effective strategy for oncotherapy, developing efficacious drug delivery systems for cancer combination therapy remains a major challenge. To improve nanodrug biocompatibility and composite function facilitating their clinical conversion application, a novel nanocarrier was presented by a facile method through conjugating humic acid with gadolinium ions to synthesize HA-Gd with good biocompatibility and dispersity. HA-Gd exhibited high photothermal conversion efficiency up to 38%, excellent photothermal stability, and high doxorubicin (DOX) loading capacity (93%) with pH-responsive release properties. HA-Gd loading DOX showed a combined chemo-photothermal inhibitory effect on tumor cells. Compared with lipid-DOX, HA-Gd-DOX had a more significant inhibitory effect on tumor growth and fewer side effects. T1-weighted MRI contrast toward tumor tissue provided HA-Gd with an MRI-based cancer diagnosis. This study revealed the great potential of humic acids as a novel vector for developing more drug carriers with desirable functions for clinical anticancer therapy.
研究领域:
医学影像
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癌症治疗
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纳米技术
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药物递送
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-14
·
IF 16.6
Gui Yueyue,Zeng Yujing,Chen Binrui,Yang Yueping,Ma Jiehua,Li Chao
Bacterial infection is a major threat to global public health, which urgently requires useful tools to rapidly analyze pathogens in the early stages of infection. Herein, we develop a smart macrophage (Mø)-based bacteria detector, which can recognize, capture, enrich and detect different bacteria and their secreted exotoxins. We transform the fragile native Møs into robust gelated cell particles (GMøs) using photo-activated crosslinking chemistry, which retains membrane integrity and recognition capacity for different microbes. Meanwhile, these GMøs equipped with magnetic nanoparticles and DNA sensing elements can not only respond to an external magnet for facile bacteria collection, but allow the detection of multiple types of bacteria in a single assay. Additionally, we design a propidium iodide-based staining assay to rapidly detect pathogen-associated exotoxins at ultralow concentrations. Overall, these nanoengineered cell particles have broad applicability in the analysis of bacteria, and could potentially be used for the management and diagnosis of infectious diseases.
研究领域:
生物技术
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纳米技术
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医学诊断
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传染病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
HUMAN GENE THERAPY
·
2023
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IF 4.2
Dr. Zhiguang Chen,Ms. Qi Zhao,Mr. Ran Zhang,Dr. Lianghong Chen,Mr. Songlan Gao,Dr. Yu Wang,Dr. Tiegang Li,Dr. Jinqi Xue
Substantial advances have been made in understanding the role of partial PDZ and LIM domain (PDLIM) family’s proteins in skeletal-related diseases. Yet, little is known about the effect of Pdlim1 on osteogenesis and fracture repair. This study aimed to investigate whether direct gene delivery using an adenovirus vector carrying Pdlim1 (Ad-oePdlim1) or encoding shRNA-Pdlim1 (Ad-shPdlim1) could affect the osteogenic activity of pre-osteoblastic MC3T3-E1 cells in vitro, and influence the fracture healing of mice in vivo. We found that Ad-shPdlim1 transfection contributed to the calcified nodule formation in MC3T3-E1 cells. Downregulation of Pdlim1 enhanced the alkaline phosphatase (ALP) activity and increased the expression of osteogenic markers (Runx2, Col1A1, osteocalcin and osteopontin). Further analysis indicated that Pdlim1 knockdown could activate β-catenin signaling, as evidenced by the accumulation of β-catenin in the nucleus and the increase levels of downstream regulators such as Lef1/Tcf7, Axin2, Cyclin D1 and Sox9. By contrast, Pdlim1 overexpression resulted in inhibition of the osteogenic activity of MC3T3-E1 cells. In vivo, at day 3 after fracture, Ad-shPdlim1 adenovirus particles were injected into the fracture site of the femur of mice, and the process of fracture healing was evaluated by X-ray, Micro-CT and histological examination. Local injection of Ad-shPdlim1 promoted the early cartilage callus formation, restored bone mineral density and accelerated cartilaginous ossification, with the upregulation of osteogenic gene (Runx2, Col1A1, osteocalcin and osteopontin) expression and activation of β-catenin signaling. Thus, we concluded that inhibition of Pdlim1 contributed to osteogenesis and fracture healing by activating the β-catenin signaling pathway.
研究领域:
分子生物学
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骨科
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再生医学
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基因治疗
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
·
IF 8.2
Shanzhu Guo,Yue Jiang,Jingjing Jiao,Yan Shi,Tao Zhu,Long Li
The spatial cellular alignment and multi-layer structure are vitally important for the physiological functions of natural blood vessels. However, the two features are difficult to be constructed in one scaffold simultaneously, especially in the small-diameter vascular scaffold. Here we report a general strategy to construct a gelatin-based biomimetic three-layer vascular scaffold with spatial alignment features mimicking the natural structure of blood vessels. By using a sequential electrospinning strategy combined with folding and rolling manipulation, a three-layer vascular scaffold with inner and middle layers spatially perpendicular to each other was obtained. The special features of this scaffold could fully mimic the natural multi-layer structures of blood vessels and also possess great potential for spatial arrangement guidance of corresponding cells in blood vessels.
研究领域:
组织工程
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生物材料
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生物医学工程
✓ 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）