课题基金基金详情
卵巢癌细胞膜伪装的共载Indoximod/DOX纳米粒构建及其靶向性和免疫抗癌作用研究
结题报告
批准号:
82002724
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
崔晓娟
依托单位:
学科分类:
肿瘤靶向治疗
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
崔晓娟
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中文摘要
免疫原性细胞死亡(ICD)与T细胞密切相关,可发挥显著抗癌作用。阿霉素(DOX)可诱导ICD,但仍有肿瘤耐药与复发,可能与免疫抑制相关。我们前期研究发现吲哚胺2,3-双加氧酶(IDO)可在肿瘤组织中高表达,影响T细胞功能及分化,引起免疫抑制;IDO抑制剂Indoximod和DOX联用可加强T细胞免疫抗癌作用。然而两药除毒性大以外尚缺乏靶向性,需要载体使两药靶向到达肿瘤部位。我们发现肿瘤细胞膜包裹的纳米粒具有良好的肿瘤靶向性。鉴此,本课题提出科学假说:卵巢癌细胞膜包裹的共载Indoximod和DOX纳米粒,可通过逆转肿瘤免疫抑制状态,增强DOX诱导的ICD,从而增加抗癌作用。研究拟通过体内外实验明确纳米粒的理化性质(包括不同pH环境进行的体外释放等)及对卵巢癌和正常细胞的靶向性,阐明载双药纳米粒对卵巢癌生长和肿瘤免疫微环境的影响及相关机制,为今后化疗和免疫治疗的联合应用提供理论和研究基础。
英文摘要
Chemotherapy-induced immunogenic cell death (ICD) plays an important role in the treatment of tumors. Doxorubicin (DOX) can induce ICD in malignant tumor, but resistance and relapse cannot be avoided. Our previous research found that Indoleamine 2,3-dioxygenase (IDO) can be highly expressed in tumor tissues, and consumes tryptophan. The combination of IDO inhibitor Indoximod and DOX can strengthen the immune and anti-cancer effect of T cells. However, in addition to its high toxicity, it lacks targeting and requires a drug carrier. We found that nanoparticles coated with tumor cell membranes have good tumor targeting. In view of this, this project proposes a scientific hypothesis: The ovarian cancer cell membrane-coated Indoximod and DOX nanoparticles can achieve tumor suppression by reversing the state of tumor immunosuppression and enhancing DOX-induced ICD. The research intends to clarify the physical and chemical properties of nanoparticles (including in vitro release by different pH solutions) and the targeting of ovarian cancer and normal cells through in vivo and in vitro experiments, and to clarify the effects of double drug-loaded nanoparticles on ovarian cancer growth and tumor immune microenvironment and its related mechanisms. The research provides a theoretical and research basis for the combined application of chemotherapy and immunotherapy in the future.
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DOI:10.1021/acsomega.1c00992
发表时间:2021-05-04
期刊:ACS omega
影响因子:4.1
作者:Cui X;Song K;Lu X;Feng W;Di W
通讯作者:Di W
DOI:--
发表时间:2023
期刊:医学综述
影响因子:--
作者:阮怡愔;崔晓娟;冯炜炜
通讯作者:冯炜炜
国内基金
海外基金