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| 1 | Injectable peptide hydrogel as intraperitoneal triptolide depot for the treatment of orthotopic hepatocellular carcinoma显示文摘Chemotherapy is among the limited choices approved for the treatment of hepatocellular carcinoma(HCC) at intermediate and advanced stages. Preferential and prolonged drug exposure in diseased sites is required to maximize the therapeutic index of the drug. Here, we report an injectable supramolecular peptide hydrogel as an intraperitoneal depot for localized and sustained release of triptolide for the treatment of orthotopic HCC. We chose peptide amphiphile C16-GNNQQNYKD-OH-based nanofibers as gelators and carriers for triptolide. Sustained triptolide release from the hydrogel was achieved over 14 days in vitro, with higher accumulation in and cytotoxicity against human HCC Bel-7402 in comparison with L-02 fetal hepatocytes. After intraperitoneal injection, the hydrogel showed prolonged retention over 13 days and preferential accumulation in the liver, realizing HCC growth inhibition by99.7 ± 0.1% and animal median survival extension from 19 to 43 days, without causing noticeable pathological changes in the major organs. These results demonstrate that injectable peptide hydrogel can be a potential carrier for localized chemotherapy of HCC. | Xiyue Zhao Xiaoyu Liu Pengcheng Zhang Yiran Liu Wei Ran Ying Cai Junyang Wang Yihui Zhai Guanru Wang Yaping Ding Yaping Li | 2019 | Acta Pharmaceutica Sinica B2019，9，5： | 7 |
| 2 | Tumor microenvironment-responsive docetaxel-loaded micelle combats metastatic breast cancer显示文摘Efficient tumor-targeting drug delivery systems are urgently needed for treating metastatic breast cancer.In this work, a docetaxel(DTX)-loaded micelle(pDM) as the tumor-microenvironment-responsive delivery platform is developed. The micelle is composed of a pH-sensitive amphiphilic copolymer,poly((1,4-butanediol)-diacrylate-b-N,N-diisopropylethylenediamine)-polyethyleneimine(BD-PEI), and a matrix metalloproteinase(MMP)-responsive polymer, poly((1,4-butanediol)-diacrylate-b-N,N-diisopropy lethylenediamine)-peptide-polyethylene glycol(PEG)(BD-peptide-PEG). The PEG block of BD-peptidePEG will be split by MMPs at the tumor microenvironment, which leads to the change of the surface charge and particle size of the micelle to more positive and smaller one. Owing to this transformation and enhanced permeability and retention(EPR) effect, pDM delivers more DTX into tumor tissues and is internalized more efficiently by tumor cells than the non-MMP-sensitive micelles in the 4 T1 tumorbearing mice model. In addition, DTX is released in acidic endo/lysosomes due to the dissociation of the micelle, triggered by the protonation of the hydrophobic block of BD-PEI. As a result, the DTX-loaded micelle inhibits primary tumor growth and pulmonary metastasis effectively. Thus, this pH/MMP-dual-sensitive drug delivery system, which simultaneously attains three keypoints: prolonged circulation time, directional and efficient uptake into tumor cells, and speedy intracellular drug release, is a promising strategy for metastatic breast cancer therapy. | Tianqun Lang Xinyue Dong Zhong Zheng Yiran Liu Guanru Wang Qi Yin Yaping Li | 2019 | Science Bulletin2019，64，2： | 5 |
| 3 | Effectiveness of flesh-moistening paste in psoriasis vulgaris patients with symptom pattern of blood stasis:a randomized and parallel-controlled trial显示文摘OBJECTIVE:To evaluate the efficacy and safety of flesh-moistening paste for treating psoriasis vulgaris in patients with blood stasis pattern in terms of Traditional Chinese Medicine(TCM).METHODS:Eudipleural rashes on both the left and right side of the same patients with psoriasis vulgaris,diagnosed via TCM as blood stasis pattern,were selected as the targeted skin lesions.A randomized,double-blind,parallel-controlled,multicenter controlled trial was conducted.The targeted skin lesions were categorized into either the treatment or control group.The treatment group used the flesh-moistening paste;the control group used a placebo.Both the paste and the placebo were topically applied twice daily for eight weeks.The patients were examined biweekly to evaluate the effects.The two groups were compared in terms of the psoriasis area and severity index(PASI)of the targeted skin lesions,which is scored according to erythema,desquamation,infiltration,area,pruritus,and improvement of skin barrier function.Adverse events were recorded during the study period.SPSS 21.0 was used to analyze the data.RESULTS:Fifty-six patients were enrolled between February 2016 and October 2017.Two were complicated by cardio-cerebrovascular disease and were excluded;thus,54 outpatients were finally enrolled in the study.Four dropped out during the study period:three failed to complete their follow-up visits for unknown reasons,and one exited due to an adverse event.The final trial comprised 50 of the 56 originally selected patients,with a 92.6%completion rate.After 8 weeks of treatment,the targeted skin lesion scores differed significantly(P<0.05).The PASI scores of the targeted skin lesions differed significantly beginning at week 6(P<0.05).The treatment group presented better results than those of the control group.Only one patient had an adverse reaction associated with the treatment.Improvements in skin barrier function differed significantly(P<0.05).CONCLUSION:The flesh-moistening paste demonstrated a reliable curative effect and safety for treating psoriasis vulgaris in patients with blood stasis patterns.The topical paste improved the barrier function of the skin lesions. | Guo Xinwei Lang Na Li Guanru Li Ping Qu Jianhua Zhou Dongmei Wang Ping Cang Zhang Deng BingXu Lou Weihai Xu Jingna Lan Haibing Liu Yumin Zhang Weishu Sun Liyun | 2020 | Journal of Traditional Chinese Medicine2020，40，6： | 4 |
| 4 | Recent advances in developing active targeting and multi-functional drug delivery systems via bioorthogonal chemistry显示文摘Bioorthogonal chemistry reactions occur in physiological conditions without interfering with normal physiological processes.Through metabolic engineering,bioorthogonal groups can be tagged onto cell membranes,which selectively attach to cargos with paired groups via bioorthogonal reactions.Due to its simplicity,high efficiency,and specificity,bioorthogonal chemistry has demonstrated great application potential in drug delivery.On the one hand,bioorthogonal reactions improve therapeutic agent delivery to target sites,overcoming off-target distribution.On the other hand,nanoparticles and biomolecules can be linked to cell membranes by bioorthogonal reactions,providing approaches to developing multi-functional drug delivery systems(DDSs).In this review,we first describe the principle of labeling cells or pathogenic microorganisms with bioorthogonal groups.We then highlight recent breakthroughs in developing active targeting DDSs to tumors,immune systems,or bacteria by bioorthogonal chemistry,as well as applications of bioorthogonal chemistry in developing functional bio-inspired DDSs(biomimetic DDSs,cell-based DDSs,bacteria-based and phage-based DDSs)and hydrogels.Finally,we discuss the difficulties and prospective direction of bioorthogonal chemistry in drug delivery.We expect this review will help us understand the latest advances in the development of active targeting and multi-functional DDSs using bioorthogonal chemistry and inspire innovative applications of bioorthogonal chemistry in developing smart DDSs for disease treatment. | Wenzhe Yi Ping Xiao Xiaochen Liu Zitong Zhao Xiangshi Sun Jue Wang Lei Zhou Guanru Wang Haiqiang Cao Dangge Wang Yaping Li | 2023 | Signal Transduction and Targeted Therapy2023，8，1： | 0 |
| 5 | A New Fiber Detection Method for LAMOST Based on the Front-illuminated Method显示文摘The double revolving fiber positioning technology is one of the key technologies for the success of the Large Sky Area Multi-Object Fiber Spectroscopic Telescope(LAMOST).The accuracy of fiber positioning will directly affect the observation efficiency of LAMOST.To achieve higher fiber positioning accuracy,the original open-loop controlled fiber positioning system urgently needs to be upgraded into a closed-loop control system.The fiber detection is the most important part of the closed-loop controlled fiber positioning system.The back-illuminated detection method is usually used to detect the fiber position by directly detecting the light spot generated at the fiber end in the multi-fiber spectral surveys.In this paper,we introduce a new method to measure the fiber position based on the image of the front-illuminated LAMOST focal plane.The front-illuminated image does not require lighting devices inside the spectrograph,and it could reduce the instability and light pollution in the spectrograph end.Our method measures the fiber position by fitting the profile of the fiber pinhole with a 2D Gaussian function.A series of tests show that the relative position measurement precision of the front-illuminated method is about 012,and the method could have the same accuracy as the back-illuminated method once the system bias is calibrated by a simple radial correction function.The required fiber positioning accuracy of LAMOST is 04,and the new method satisfies the requirement of LAMOST fiber detection accuracy and could be used in the closed-loop fiber control system. | Ming Zhou Yong Zhang Guanru Lv Jian Li Zengxiang Zhou Zhigang Liu Jianping Wang Zhongrui Bai Yuan Tian Mengxin Wang Shuqing Wang Hongzhuan Hu Chao Zhai Jiaru Chu Zhijie Han Mingxu Liu Yiqiao Dong Hailong Yuan Yongheng Zhao Yaoquan Chu Haotong Zhang | 2022 | Research in Astronomy and Astrophysics2022，22，6： | 0 |
| 6 | Long non-coding RNA colon cancer-associated transcript 2:role and function in human cancers显示文摘Long non-coding RNAs(lncRNAs)are a family of non-protein-coding RNAs that span a length of over 200 nucleotides.Research reports have illustrated that lncRNAs are involved in various cellular processes and that their abnormal expression leads to the occurrence and development of various tumors.Colon cancer-associated transcript 2(CCAT2)was first reported as an oncogene in colon cancer.LncRNA CCAT2 is abnormally expressed in hepatocellular carcinoma,cholangiocarcinoma,lung cancer,breast cancer,ovarian cancer,glioma,and other tumors.In tumor tissues,abnormally overexpressed CCAT2 can affect cell proliferation,migration,epithelial-mesenchymal transition,apoptosis,and other biological behaviors through endogenous RNAs mechanisms,various signaling pathways,transcriptional regulation,and other complex mechanisms.Additionally,the overexpression of CCAT2 is also closely related to the tumor size,tumor node metastasis(TNM)stage,survival time,and other prognostic factors,suggesting that it is a potential prognostic indicator.This article reviews the biological functions of CCAT2 and its mechanisms of action in tumors from previous studies.In this review,we attempt to provide a molecular basis for future clinical applications of lncRNA CCAT2. | Shuoshuo Ma Wenjing Wang Dengyong Zhang Guanru Zhao Zheng Lu | 2022 | Chinese Medical Journal2022，135，23： | 0 |
| 7 | Acid-switchable nanoparticles induce self-adaptive aggregation for enhancing antitumor immunity of natural killer cells显示文摘Deficiency of natural killer(NK)cells shows a significant impact on tumor progression and failure of immunotherapy.It is highly desirable to boost NK cell immunity by upregulating active receptors and relieving the immunosuppressive tumor microenvironment.Unfortunately,mobilization of NK cells is hampered by poor accumulation and short retention of drugs in tumors,thus declining antitumor efficiency.Herein,we develop an acid-switchable nanoparticle with self-adaptive aggregation property for co-delivering galunisertib and interleukin 15(IL-15).The nanoparticles induce morphology switch by a decomposition-metal coordination cascade reaction,which provides a new methodology to trigger aggregation.It shows self-adaptive size-enlargement upon acidity,thus improving drug retention in tumor to over 120 h.The diameter of agglomerates is increased and drug release is effectively promoted following reduced p H values.The nanoparticles activate both NK cell and CD8+T cell immunity in vivo.It significantly suppresses CT26 tumor in immune-deficient BALB/c mice,and the efficiency is further improved in immunocompetent mice,indicating that the nanoparticles can not only boost innate NK cell immunity but also adaptive T cell immunity.The approach reported here provides an innovative strategy to improve drug retention in tumors,which will enhance cancer immunotherapy by boosting NK cells. | Xiangshi Sun Xiaoxuan Xu Jue Wang Xinyue Zhang Zitong Zhao Xiaochen Liu Guanru Wang Lesheng Teng Xia Chen Dangge Wang Yaping Li | 2023 | Acta Pharmaceutica Sinica B2023，13，7： | 0 |
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