CN112494645A - 一种砷烯纳米材料与免疫检查点抑制剂联合应用于肿瘤治疗 - Google Patents
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Abstract
本发明提供一种砷烯纳米材料与免疫检查点抑制剂联合应用于肿瘤治疗，具体涉及生物医药技术领域，砷烯纳米材料与PD‑1抗体联合用于抑制宫颈癌肿瘤；砷烯纳米材料能够在体内激活免疫反应，与PD‑1抗体联用后明显增强PD‑1抗体的抑瘤效果。本发明将砷烯作为PD‑1抗体免疫治疗的辅助纳米药物起到更高效地抑制肿瘤的作用。
Description
技术领域
本发明属于生物医药技术领域，具体涉及一种砷烯纳米材料与免疫检查点抑制剂联合应用于肿瘤治疗。
背景技术
免疫检查点抑制剂疗法通过释放患者自身的T细胞来杀死肿瘤，目前主要适用于免疫原性肿瘤如黑色素瘤、肾癌以及非小细胞肺癌。程序性死亡受体1(programmed death1,PD-1)及其配体(programmed death 1 ligand，PD-L1)是目前研究最为广泛的免疫检查点。
PD-1途径是肿瘤微环境局部免疫抑制的关键介质，也可以调节次级淋巴组织中针对肿瘤抗原的T细胞启动。在其他治疗无效的晚期不能手术的癌症中，阻断淋巴细胞上的PD-1受体或肿瘤上PD-L1配体的药物能够介导肿瘤的消退。
目前已有大量针对此免疫检查点研究获得的单克隆抗体出现。第一个靶向免疫检查点PD-1的单克隆抗体抑制剂Pembrolizumab在2016年上市，用于晚期黑色素瘤和非小细胞肺癌的治疗。随后发展的Nivolumab,Atezolizumab,Avelumab以及Durvalumab对肾细胞癌、尿路上皮癌和非小细胞肺癌具有显著治疗效果。
近几十年来，纳米粒子因其易修饰、生物相容性和固有的肿瘤靶向性而被证明是一种有效的药物传递工具，并已被应用于肿瘤免疫治疗。通过将增强渗透性和保留性(EPR)介导的被动靶向与肿瘤和淋巴器官中的前体单核细胞、肿瘤相关巨噬细胞(TAMs)、肿瘤浸润性T细胞(TIT)和树突状细胞(DCs)等多种免疫细胞的配体相结合，开发纳米颗粒辅助肿瘤免疫治疗。
发明内容
为了拓展砷烯在生物医学领域的应用，本发明的目的在于提供一种砷烯纳米材料的应用，包含砷烯与PD-1抗体的联用促进PD-1抗体的免疫治疗。所述促进PD-1抗体的免疫治疗的功能主要表现在比普通的PD-1抗体疗法抑制肿瘤作用明显增强。
本发明提供了如下的技术方案：
一种砷烯纳米材料与免疫检查点抑制剂联合应用于肿瘤治疗，其特征在于，砷烯纳米材料与PD-1抗体联合用于宫颈癌的肿瘤抑制；
优选的，砷烯纳米材料制备：将500毫克纯砷粉，分散在20mL纯度99.99％为二甲基亚砜中；并通入氮气10min将系统中的氧气排出；在功率为1700W的YMN1-1800Y超声波细胞研磨机中冰浴120min进行剥离得到分散体，DMSO洗涤三次以去除超声过程中产生的杂质，6000rpm转速离心2分钟，收集上清，获得砷烯纳米材料；
再将砷烯纳米材料与PD-1抗体联用。
优选的，砷烯纳米材料与PD-1抗体联用，具体如下：将受体注射0.67mg/Kg的砷烯纳米材料和10mg/Kg anti-PD-1抗体注射液。
本发明的有益效果：
本发明砷烯与PD-1抗体的联用促进PD-1抗体的免疫治疗的用途，砷烯纳米材料在小鼠体内能够抑制肿瘤表面免疫检查点PD-1与PD-L1的结合，利用这一特性，可以将砷烯作为PD-1抗体免疫治疗的辅助纳米药物起到更高效地治疗肿瘤的作用；砷烯纳米材料能够在体内激活免疫反应，与PD-1抗体联用后明显增强PD-1抗体的抑瘤效果。
附图说明
附图用来提供对本发明的进一步理解，并且构成说明书的一部分，与本发明的实施例一起用于解释本发明，并不构成对本发明的限制。在附图中：
图1为本发明实施例1所用疗法处理后U14荷瘤小鼠肿瘤组织示意图；
图2为本发明实施例1所用疗法处理后U14荷瘤小鼠瘤体积变化示意图；
图3为本发明实施例1所用疗法处理后U14荷瘤小鼠体重变化示意图。
具体实施方式
实施例1：
砷烯纳米材料与PD-1抗体共同给药
S1、向雌性Balb/c小鼠前肢皮下植入鼠源宫颈癌U14细胞，建立小鼠宫颈癌模型，一周后取成瘤小鼠分3笼，每笼5只。
S2、对照组注射100μL PBS溶液，实验组分别注射10mg/Kg anti-PD-1抗体注射液和同时注射0.67mg/Kg的砷烯纳米材料和10mg/Kg anti-PD-1抗体注射液。
实施例2：砷烯与PD-1抗体的联用的抑制肿瘤实验
S1、每日对实施例1疗法处理的小鼠进行体重和瘤体积测量，记录数据，连续两周。
S2、两周后将小鼠断颈处死，解剖获取皮下肿瘤组织，测量比较最终瘤体积，记录数据，具体实验数据参见附图1、附图2、附图3。
以上仅为本发明的优选实施例而已，并不用于限制本发明，尽管参照前述实施例对本发明进行了详细的说明，对于本领域的技术人员来说，其依然可以对前述各实施例所记载的技术方案进行修改，或者对其中部分技术特征进行等同替换。凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。
Claims (3)
1.一种砷烯纳米材料与免疫检查点抑制剂联合应用于肿瘤治疗，其特征在于：砷烯纳米材料与PD-1抗体联用用于PD-1抗体的抑瘤。
2.根据权利要求1所述的一种砷烯纳米材料与免疫检查点抑制剂联合应用于肿瘤治疗，其特征在于：
砷烯纳米材料制备：将500毫克纯砷粉，分散在20mL纯度99.99％为二甲基亚砜中；并通入氮气10min将系统中的氧气排出；在功率为1700W的YMN1-1800Y超声波细胞研磨机中冰浴120min进行剥离得到分散体，DMSO洗涤三次以去除超声过程中产生的杂质，6000rpm转速离心2分钟，收集上清，获得砷烯纳米材料；
再将砷烯纳米材料与PD-1抗体联用。
3.根据权利要求2所述的一种砷烯纳米材料与免疫检查点抑制剂联合应用于肿瘤治疗，其特征在于：砷烯纳米材料与PD-1抗体联用，具体如下：将受体注射0.67mg/Kg的砷烯纳米材料和10mg/Kg anti-PD-1抗体注射液。
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2016019232A1 (en) * | 2014-08-01 | 2016-02-04 | John Vasilakos | Methods and therapeutic combinations for treating tumors |
| WO2018113258A1 (zh) * | 2016-12-22 | 2018-06-28 | 安源医药科技（上海）有限公司 | 抗pd-1抗体及其用途 |
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| WO2016019232A1 (en) * | 2014-08-01 | 2016-02-04 | John Vasilakos | Methods and therapeutic combinations for treating tumors |
| WO2018113258A1 (zh) * | 2016-12-22 | 2018-06-28 | 安源医药科技（上海）有限公司 | 抗pd-1抗体及其用途 |
Non-Patent Citations (2)
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| WANG XX等: "Arsenene:a potential therapeutic agent for acute promyelocytic leukaemia cells by acting on nuclear proteins", ANGEWANDTE CHEMIE INTERNATIONAL EDITION, vol. 59, no. 13, pages 5151 - 5158, XP072099204, DOI: 10.1002/anie.201913675 * |
| 徐苗等: "PD-1/PD-L1信号通路抑制剂在宫颈癌治疗中的研究进展", 万方, vol. 31, no. 5, pages 418 - 420 * |
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