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| 1 | Menthol-modified casein nanoparticles loading 10-hydroxycamptothecin for glioma targeting therapy显示文摘Chemotherapy outcomes for the treatment of glioma remains unsatisfactory due to the inefficient drug transport across the blood–brain barrier(BBB) and insufficient drug accumulation in the tumor region. Although many approaches, including various nanosystems, have been developed to promote the distribution of chemotherapeutics in the brain tumor, the delivery efficiency and the possible damage to the normal brain function still greatly restrict the clinical application of the nanocarriers.Therefore, it is urgent and necessary to discover more safe and effective BBB penetration and gliomatargeting strategies. In the present study, menthol, one of the strongest BBB penetration enhancers screened from traditional Chinese medicine, was conjugated to casein, a natural food protein with brain targeting capability. Then the conjugate self-assembled into the nanoparticles to load anti-cancer drugs.The nanoparticles were characterized to have appropriate size, spheroid shape and high loading drug capacity. Tumor spheroid penetration experiments demonstrated that penetration ability of mentholmodified casein nanoparticles(M-CA-NP) into the tumor were much deeper than that of unmodified nanoparticles. In vivo imaging further verified that M-CA-NPs exhibited higher brain tumor distribution than unmodified nanoparticles. The median survival time of glioma-bearing mice treated with HCPT-MCA-NPs was significantly prolonged than those treated with free HCPT or HCPT-CA-NPs. HE staining ofthe organs indicated the safety of the nanoparticles. Therefore, the study combined the advantages of traditional Chinese medicine strategy with modern delivery technology for brain targeting, and provide a safe and effective approach for glioma therapy. | Caifang Gao Jianming Liang Ying Zhu Chengli Ling Zhekang Cheng Ruixiang Li Jing Qin Weigen Lu Jianxin Wang | 2019 | Acta Pharmaceutica Sinica B2019，9，4： | 12 |
| 2 | A novel tumor-targeting treatment strategy uses energy restriction via co-delivery of albendazole and nanosilver显示文摘尽管纳米技术很快在指向的肿瘤被开发了并且适用,化疗的结果仍然保持极大地在正常纸巾和房间由细胞毒素的药的毒性限制了。因此,与在正常房间的很少副作用,其他的交货系统的开发吸引了增加的注意。精力限制是癌症治疗的一条新奇、有希望的途径,它能经由细胞的精力新陈代谢的抑制限制肿瘤生长。在这研究,指向系统的一个新奇肿瘤,基于叶酸结合牛的浆液白朊(BSA ) ,被开发到共同交付 albendazole 和 nanosilver 同时,制止肿瘤房间的精力新陈代谢。没有 folic 酸修正, nanosilver,或 albendazole,这 nanosystem 用 nanoparticles 比那些显示出更强壮的反肿瘤功效,在 vitro 并且在 vivo。这 nanosystem 弄空经由 glycolytic 酶和 mitochondrial 损坏的直接抑制的细胞的 ATP,导致肿瘤房间的增长,房间周期拘捕,和 apoptosis 的抑制。提高的反肿瘤活动贡献了这个系统的指向肿瘤的能力,导致在肿瘤房间的特定的精力抑制。毒性评估被执行证实这个系统的安全。这 nanosystem 为肿瘤治疗提供有效、安全的策略。 | Jianming Liang Ruixiang Li Yuwei He Chengli Ling Qi Wang Yongzhuo Huang Jing Qin Weigen Lu Jianxin Wang | 2018 | Nano Research2018，11，9： | 3 |
| 3 | DNA crosslinking and recombination-activating genes 1/2(RAG1/2)are required for oncogenic splicing in acute lymphoblastic leukemia显示文摘Background:Abnormal alternative splicing is frequently associated with carcinogenesis.In B-cell acute lymphoblastic leukemia(B-ALL),double homeobox 4 fused with immunoglobulin heavy chain(DUX4/IGH)can lead to the aberrant production of E-26 transformation-specific family related gene abnormal transcript(ERGalt)and other splicing variants.However,the molecular mechanism underpinning this process remains elusive.Here,we aimed to know how DUX4/IGH triggers abnormal splicing in leukemia.Methods:The differential intron retention analysis was conducted to identify novel DUX4/IGH-driven splicing in B-ALL patients.X-ray crystallography,small angle X-ray scattering(SAXS),and analytical ultracentrifugation were used to investigate how DUX4/IGH recognize double DUX4 responsive element(DRE)-DRE sites.The ERGalt biogenesis and B-cell differentiation assays were performed to characterize the DUX4/IGH crosslinking activity.To check whether recombination-activating gene 1/2(RAG1/2)was required for DUX4/IGH-driven splicing,the proximity ligation assay,co-immunoprecipitation,mammalian two hybrid characterizations,in vitro RAG1/2 cleavage,and shRNA knock-down assays were performed.Results:We reported previously unrecognized intron retention events in Ctype lectin domain family 12,member A abnormal transcript(CLEC12Aalt)and chromosome 6 open reading frame 89 abnormal transcript(C6orf89alt),where also harbored repetitive DRE-DRE sites.Supportively,X-ray crystallography and SAXS characterization revealed that DUX4 homeobox domain(HD)1-HD2 might dimerize into a dumbbell-shape trans configuration to crosslink two adjacent DRE sites.Impaired DUX4/IGH-mediated crosslinking abolishes ERGalt,CLEC12Aalt,and C6orf89alt biogenesis,resulting in marked alleviation of its inhibitory effect on B-cell differentiation.Furthermore,we also observed a rare RAG1/2-mediated recombination signal sequence-like DNA edition in DUX4/IGH target genes.Supportively,shRNA knock-down of RAG1/2 in leukemic Reh cells consistently impaired the biogenesis of ERGalt,CLEC12Aalt,and C6orf89alt.Conclusions:All these results suggest that DUX4/IGH-driven DNA crosslinking is required for RAG1/2 recruitment onto the double tandem DRE-DRE sites,catalyzing V(D)J-like recombination and oncogenic splicing in acute lymphoblastic leukemia. | Hao Zhang Nuo Cheng Zhihui Li Ling Bai Chengli Fang Yuwen Li Weina Zhang Xue Dong Minghao Jiang Yang Liang Sujiang Zhang Jianqing Mi Jiang Zhu Yu Zhang Sai-Juan Chen Yajie Zhao Xiang-Qin Weng Weiguo Hu Zhu Chen Jinyan Huang Guoyu Meng | 2021 | Cancer Communications2021，41，11： | 0 |
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