基于敲减三阴性乳腺癌趋化因子受体CCR4的自封孔纳米羟基磷灰石材料的靶向治疗研究

批准号:
81501537
项目类别:
青年科学基金项目
资助金额:
18.0 万元
负责人:
刘莹
依托单位:
学科分类:
H2706.分子影像
结题年份:
2018
批准年份:
2015
项目状态:
已结题
项目参与者:
程晓青、王春艳、孙晶、苏云燕、谢媛
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中文摘要
缺乏明确有效的治疗靶点是三阴性乳腺癌(TNBC)治疗的瓶颈,探索靶向、高效、安全的药物是其难点。研究表明趋化因子受体CCR4在TNBC发生、发展和转移中均起重要作用,可能成为TNBC治疗的新靶点,RNA干扰抑制CCR4表达将会提高TNBC的治疗疗效。为了高效安全递送小干扰RNA(siRNA)抑制CCR4的表达,我们拟研制自封孔的纳米羟基磷灰石材料,实现pH刺激响应性递送siRNA。又因TNBC细胞表面高表达整合素αvβ3,环化肽c(RGDFK)可与其特异性结合,连接c(RGDFK)能靶向到肿瘤细胞。因此,本项目拟以CCR4为治疗靶点,环化肽c(RGDFK)为识别分子,自封孔纳米羟基磷灰石为载体,递送可敲减CCR4的siRNA和抗癌药物阿霉素靶向治疗TNBC,并结合磁共振/光学成像技术进行实时监测和评估治疗,预期提高TNBC的治疗疗效,为临床TNBC的治疗提供新的方法和疗效检测手段。
英文摘要
Triple negative breast cancer (TNBC) is very difficult to treat due to the lack of effective therapeutic targets. It is necessary to develop new targeted drug delivery systems to improve efficacy. Studies have shown that CCR4 plays an important role in the development and metastasis of TNBC, and is a promising new target for TNBC. Nano-hydroxyapatite(NHAP)can protect loaded drugs form premature release during the circulation and then release drugs in the tumor-specific acidic environment after capped by itself. Therefore, it can be used as a carrier to delivery drugs for on-demand release at tumor site and small interfering RNA (siRNA) of CCR4 expression to improve the efficacy and reduce toxicity. This project intends to build new NHAP drug carriers loaded CCR4 and doxorubicin to recognize c(RGDFK) and for targeting and CCR4 for therapy. Then investigate the delivery efficiency and controlled-release profiles of siRNA and doxorubicin in TNBC cell lines and xenografts in situ. Furthermore, combine with MRI and fluorescence imaging to real-time monitor distribution and treatment efficacy for TNBC. The project is expected to construct a new anticancer drug system for target therapy and efficacy monitor of TNBC.
缺乏明确有效的治疗靶点是三阴性乳腺癌(TNBC)治疗的瓶颈,探索靶向、高效、安全的药物是其难点。研究表明XBP1在TNBC发生、发展和转移中均起重要作用,有可能成为TNBC的新靶点;纳米羟基磷灰石(NHAP)可在肿瘤特有的微酸环境下降解实现高效安全递药。本项目以XBP1为治疗靶点,环化肽c(RGDFK)为识别分子,利用装载抗癌药物阿霉素(DOX)和可敲减XBP1的siRNA的NHAP对TNBC治疗进行研究,通过RNA干扰抑制XBP1表达和可控释放DOX联合治疗TNBC, 并结合磁共振/光学成像技术进行监测和评估治疗,提高TNBC的治疗疗效,并抑制了转移,为临床TNBC的分子靶向治疗及磁共振成像提供手段和奠定基础。
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
Periodic Mesoporous Organosilica Coated Prussian Blue for MR/PA Dual-Modal Imaging-Guided Photothermal-Chemotherapy of Triple Negative Breast Cancer.
周期性介孔有机硅涂层普鲁士蓝用于 MR/PA 双模态成像引导三阴性乳腺癌光热化疗
DOI:10.1002/advs.201600356
发表时间:2017-03
期刊:Advanced science (Weinheim, Baden-Wurttemberg, Germany)
影响因子:--
作者:Tian W;Su Y;Tian Y;Wang S;Su X;Liu Y;Zhang Y;Tang Y;Ni Q;Liu W;Dang M;Wang C;Zhang J;Teng Z;Lu G
通讯作者:Lu G
Synergistic Chemo-Photothermal Therapy of Breast Cancer by Mesenchymal Stem Cell-Encapsulated Yolk-Shell GNR@HPMO-PTX Nanospheres.
间充质干细胞包裹卵黄壳 GNR@HPMO-PTX 纳米球协同化疗光热治疗乳腺癌
DOI:10.1021/acsami.6b05677
发表时间:2016
期刊:ACS Applied Mater Interfaces
影响因子:--
作者:Wu Jiang;Liu Ying;Tang Yuxia;Wang Shouju;Wang Chunyan;Li Yanjun;Su Xiaodan;Tian Jihong;Tian Ying;Pan Jing;Su Yunyan;Zhu Hong;Teng Zhaogang;Lu Guangming
通讯作者:Lu Guangming
Photosensitizer-loaded biomimetic platform for multimodal imaging-guided synergistic phototherapy.
用于多模态成像引导协同光疗的光敏剂仿生平台
DOI:10.1039/c8ra04663h
发表时间:2018-09-12
期刊:RSC ADVANCES
影响因子:3.9
作者:Tian, Ying;Zhao, Ying;Liu, Wenfei;Liu, Ying;Tang, Yuxia;Teng, Zhaogang;Zhang, Chunni;Wang, Shouju;Lu, Guangming
通讯作者:Lu, Guangming
Depletion of collagen by losartan to improve tumor accumulation and therapeutic efficacy of photodynamic nanoplatforms
氯沙坦消耗胶原蛋白以改善肿瘤积累和光动力纳米平台的治疗效果
DOI:10.1007/s13346-018-00610-1
发表时间:2019-06-01
期刊:DRUG DELIVERY AND TRANSLATIONAL RESEARCH
影响因子:5.4
作者:Tang, Yuxia;Liu, Ying;Lu, Guangming
通讯作者:Lu, Guangming
Gadolinium-Doped Hydroxyapatite Nanorods as T1 Contrast Agents and Drug Carriers for Breast Cancer Therapy
掺钆羟基磷灰石纳米棒作为 T1 造影剂和药物载体用于乳腺癌治疗
DOI:10.1021/acsanm.8b02036
发表时间:2019-03-01
期刊:ACS APPLIED NANO MATERIALS
影响因子:5.9
作者:Liu, Ying;Tang, Yuxia;Lu, Guangming
通讯作者:Lu, Guangming
国内基金
海外基金
