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C6细胞
Molecular Medicine Reports · 2017 ·Vol. 16 ·期 6 ·9401-9408 · IF 1.692

Hyperthermia with different temperatures inhibits proliferation and promotes apoptosis through the EGFR/STAT3 pathway in C6 rat glioma cells

Yao‑Dong Chen,Yu Zhang,Tian‑Xiu Dong,Yu‑Tong Xu,Wei Zhang,Ting‑Ting An,Peng‑Fei Liu,Xiu‑Hua Yang

Malignant gliomas are a group of aggressive neoplasms among human cancers. The curative effects of current treatments are finite for improving the prognosis of patients. Hyperthermia (HT) is an effective treatment for cancers; however, the effects of HT with different temperatures in treatment of MG and relevant mechanisms remain unclear. MTT assay and Annexin V‑fluorescein isothiocyanate/propidium iodide staining were used for investigating the proliferation and apoptosis of C6 cells, respectively. Western blotting was applied to detect the expression of proteins. Ultrasonography was employed to evaluate the tumor formation rate, growth rate, angiogenesis rate and degree of hardness of tumors in vivo. The authors certified that HT with 42‑46˚C x 1 h, 1 t could inhibit proliferation, promote apoptosis, reduce tumor formation rate, growth rate, angiogenesis rate, degree of hardness of tumors, ischemic tolerance and anoxic tolerance, and have synergy with temozolomide in C6 cells. Long‑term HT (43˚C x 1 h, 1 t/5 d, 90 d) did not cut down the sensitivity of C6 cells to HT, and sustainably inhibited the proliferation of C6 cells. Furthermore, the authors proved HT produced these effects primarily through inhibition of the EGFR/STAT3/HIF‑1A/VEGF‑A pathway.

CAS / MDL: 85622-93-1
研究领域: 肿瘤学 · 细胞生物学 · 分子生物学
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY · 2015 · IF 0.476

Antitumor activity of transferrin-modified- artemether lipid nanospheres in cancer cell lines

S.E. Eltayeb,Zhigui Su,Yanyu Xiao,Qineng Ping

Diverse lines of research show that the cellular response to artemether (ART) is multi-factorial in nature. The cytotoxicity of ART is specific to cancer cells because most of them over expressed; transferrin receptors and have high level of intracellular iron and ART is mainly toxic after; interaction with iron ion. Our aim is to investigate the effect of some formulation characteristics on; the cytotoxicity of ART in C6 and MCF-7 cells lines. In this study, the cytotoxicity of ART-loaded; anionic, cationic or neutral (transferrin modified) lipid nanospheres was studied by MTT and; apoptosis tests. Characterizations of apoptosis were done. The effect on the mitochondria and the; nucleus was qualitatively characterized after using different types of cell tracker dyes. The cellular; uptake, accumulation and distribution of the formulations were characterized after loading; different hydrophobic fluorescence probes instead of ART. The relation between the; accumulated amount of ART and its cytotoxicity was defined. Our study shows that ART can be highly toxic to the tumor cells if accumulated in a large amount in the cell. Lipid nanosphere containing tween80 and transferrin can highly accumulate ART in brain cells and can be; formulated as a promising potent, safe and inexpensive drug carriers for brain tumors.

研究领域: 药理学 · 肿瘤学 · 纳米技术
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EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES · 2022 · IF 5.112

Preparation of C6 cell membrane-coated doxorubicin conjugated manganese dioxide nanoparticles and its targeted therapy application in glioma

Jiaqun Du,Junpeng Sun,Xiaobang Liu,Qian Wu,Wenwen Shen,Yu Gao,Ying Liu,Chao Wu

In this study, we prepared a C6 cell membrane-coated doxorubicin conjugated manganese dioxide biomimetic nanomedicine system (MnO 2 -DOX-C6) for the treatment of glioma. In the glioma microenvironment, manganese dioxide could alleviate tumor hypoxia by promoting the decomposition of hydrogen peroxide (H 2 O 2 ) to generate oxygen and, through a Fenton-like reaction, increase ROS levels in tumor cells, thus inducing oxidative stress to further kill cancer cells. Doxorubicin and manganese dioxide were connected through a hydrazone bond so that doxorubicin could be released only in the acidic environment of the tumor, which helped to reduce the toxicity and side effects of doxorubicin. Encapsulation of glioma C6 cancer cell membrane in MnO 2 -DOX-C6 made MnO 2 -DOX possess the homologous targeting ability and also regulated drug release rate. In vitro release experiments showed that the cumulative release of doxorubicin from MnO 2 -DOX-C6 at a pH of 5.0 for 48 h was 66.84 ± 3.81%, proving that it had pH sensitivity and a sustained-release effect. Cellular uptake experiments showed that MnO 2 -DOX-C6 had a good ability to target syngeneic tumor cells. MTT, flow cytometry, Western blot, cell immunofluorescence staining and in vivo antitumor experiments demonstrated that MnO 2 -DOX-C6 could promote C6 cell apoptosis and inhibit its proliferative ability. These results clearly suggested that MnO 2 -DOX-C6 may be a promising bionic nanosystem agent for the treatment of glioma.

研究领域: 纳米技术 · 药学 · 肿瘤学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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DRUG DELIVERY · 2018 · IF 3.095

Nose-to-brain delivery of temozolomide-loaded PLGA nanoparticles functionalized with anti-EPHA3 for glioblastoma targeting

Liuxiang Chu,Aiping Wang,Ling Ni,Xiuju Yan,Yina Song,Mingyu Zhao,Kaoxiang Sun,Hongjie Mu,Sha Liu,Zimei Wu,Chunyan Zhang

Glioblastoma is the most common malignant brain tumor. Efficient delivery of drugs targeting glioblastomas remains a challenge. Ephrin type-A receptor 3 (EPHA3) tyrosine kinase antibody-modified polylactide-co-glycolide (PLGA) nanoparticles (NPs) were developed to target glioblastoma via nose-to-brain delivery. Anti-EPHA3-modified, TBE-loaded NPs were prepared using an emulsion-solvent evaporation method, showed a sustained in vitro release profile up to 48 h and a mean particle size of 145.9 ± 8.7 nm. The cellular uptake of anti-EPHA3-modified NPs by C6 cells was significantly enhanced compared to that of nontargeting NPs (p < .01). In vivo imaging and distribution studies on the glioma-bearing rats showed that anti-EPHA3-modified NPs exhibited high fluorescence intensity in the brain and effectively accumulated to glioma tissues, indicating the targeting effect of anti-EPHA3. Glioma-bearing rats treated with anti-EPHA3-modified NPs resulted in significantly higher tumor cell apoptosis (p < .01) than that observed with other formulations and prolonged the median survival time of glioma-bearing rats to 26 days, which was 1.37-fold longer than that of PLGA NPs. The above results indicated that anti-EPHA3-modified NPs may potentially serve as a nose-to-brain drug carrier for the treatment of glioblastoma.

研究领域: 神经学 · 药剂学 · 肿瘤学 · 纳米技术 · 药物递送系统
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JOURNAL OF NANOBIOTECHNOLOGY · 2021 ·Vol. 19 ·期 1 ·1-24 · IF 10.435

Hybrid membrane-coated nanosuspensions for multi-modal anti-glioma therapy via drug and antigen delivery

Hao Wenyan,Cui Yuexin,Fan Yueyue,Chen Mengyu,Yang Guobao,Wang Yuli,Yang Meiyan,Li Zhiping,Gong Wei,Yang Yang,Gao Chunsheng

Background Glioma is one of the deadliest human cancers. Although many therapeutic strategies for glioma have been explored, these strategies are seldom used in the clinic. The challenges facing the treatment of glioma not only involve the development of chemotherapeutic drugs and immunotherapeutic agents, but also the lack of a powerful platform that could deliver these two moieties to the targeted sites. Herein, we developed chemoimmunotherapy delivery vehicles based on C6 cell membranes and DC membranes to create hybrid membrane-coated DTX nanosuspensions (DNS-[C6&DC]m). Results Results demonstrated successful hybrid membrane fusion and nanosuspension functionalization, and DNS-[C6&DC]m could be used for different modes of anti-glioma therapy. For drug delivery, membrane coating could be applied to target the source cancer cells via a homotypic-targeting mechanism of the C6 cell membrane. For cancer immunotherapy, biomimetic nanosuspension enabled an immune response based on the professional antigen-presenting characteristic of the dendritic cell membrane (DCm), which carry the full array of cancer cell membrane antigens and facilitate the uptake of membrane-bound tumor antigens for efficient presentation and downstream immune n. Conclusion DNS-[C6&DC]m is a multifunctional biomimetic nano-drug delivery system with the potential to treat gliomas through tumor-targeted drug delivery combined with immunotherapy, thereby presenting a promising approach that may be utilized for multiple modes of cancer therapy. Graphical Abstract

研究领域: 肿瘤学 · 药学 · 免疫疗法 · 纳米技术
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS · 2018 · IF 2.559

Combination of 3-methyladenine therapy and Asn-Gly-Arg (NGR)-modified mesoporous silica nanoparticles loaded with temozolomide for glioma therapy in vitro

Peng Zhang,Menghuan Tang,Qin Huang,Guanjian Zhao,Ning Huang,Xiang Zhang,Ying Tan,Yuan Cheng

Mesoporous silica nanoparticles (MSNPs) of a small diameter were loaded with the anticancer drug temozolomide (TMZ), coated with polydopamine (PDA), and conjugated with Asn-Gly-Arg (NGR) for use in the treatment of glioma. The accumulation of NGR-MSNPs in C6 cells was shown to be higher than that of unmodified MSNPs. Anticancer drugs can cause autophagy in tumor cells, whereas autophagy inhibitors can block this reaction and enhance the therapeutic effect of the drugs. In this study, we demonstrated that MSNP-TMZ-PDA-NGR had stronger autophagy- and apoptosis-inducing effects in C6 cells than TMZ alone, and its anticancer effect was further enhanced when combined with autophagy inhibition. These results demonstrate that the combination of targeting vehicles and autophagy inhibitors may have research value in the treatment of gliomas.

CAS / MDL: 62-31-7 989-38-8
研究领域: 纳米技术 · 药学 · 肿瘤学 · 细胞生物学
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Nano Energy · 2021 · IF 17.881

Ultrasound-activated Au/ZnO-based Trojan nanogenerators for combined targeted electro-stimulation and enhanced catalytic therapy of tumor

Kongshuo Ma,Guohua Qi,Bo Wang,Tengfei Yu,Ying Zhang,Haijuan Li,Shimeles Addisu Kitte,Yongdong Jin

Integrating the advantages of multiple therapies into one therapeutic platform is highly desired for augmented treatment effects. Herein, by modifying MLS and PEG on ZnO-nanorods/AuNPs nanoassemblies and coating with C6 cell membrane (MP-Au/ [email protected] ), we construct a novel ultrasound-activatable Au/ZnO-based tumor therapeutic platform (Trojan nanogenerators) and exploit it for effective tumor therapy. The developed MP-Au/ [email protected] nanogenerators worked well in multiple ways to achieve targeted electrostimulation and enhanced catalytic therapy of tumor, under ultrasound excitation. Firstly, the ZnO-nanogenerators will generate a piezoelectric potential difference of about 140 mV by ultrasonic excitation when targeted (by MLS moiety) to the mitochondria, disrupting the mitochondrial membrane potential for electrostimulation. Secondly, the nanogenerators enhances greatly multiple enzyme-like activities of Au nano-components for enhanced tumor catalytic therapy. Among them, the affinity and maximum reaction rate of peroxidase-like are increased by 34.99% and 53.36% respectively through kinetic analysis . Simulations and calculations revealed the roles of piezoelectric polarization electric field and displacement current in enhancing catalytic activity . The superior tumor suppressive effect of the MP-Au/ [email protected] was confirmed by in-vitro cell study and in-vivo C6 tumor-bearing mouse models. The developed ultrasound-activated nanogenerators will provide a unique electrostimulation tumor therapy strategy and opens a new way for improving the therapeutic efficacy of nanozymes.

研究领域: 生物医学工程 · 纳米技术 · 癌症治疗 · 材料科学
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