CN116063245A - 一种中心可降解的mRNA脂质体纳米粒子及其制备方法和应用 - Google Patents
一种中心可降解的mRNA脂质体纳米粒子及其制备方法和应用 Download PDFInfo
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Abstract
Description
技术领域
本发明涉及新材料及生物技术领域,具体涉及一种具有不同器官靶向性中心可降解的mRNA脂质体纳米粒子及其制备方法和应用。
背景技术
基因治疗是指通过特定的方法将功能性核酸分子递送至靶细胞,提供、纠正或补偿相关致病基因,在多种疾病中具有广泛应用。其中,由于信使RNA(mRNA)只需要到达细胞质就能产生功能蛋白,相对于DNA治疗方案降低了插入突变的风险,而且具有更高的转染效率,因此在由异常蛋白表达引起的许多疾病的治疗上吸引了研究者们的极大关注。但是,单独的mRNA是一条长链柔性分子,会被血液循环中核酸酶所降解,极其不稳定;且mRNA自身带负电荷,导致其不容易穿过细胞膜进入特定细胞内。因此,开发安全高效的mRNA载体具有十分重要的意义。
相对于病毒载体,非病毒载体具有安全,易制备,低免疫原性等优点。其中,已有多种脂质纳米颗粒(LNPs)被用于mRNA的体内传递。尽管脂质体纳米粒子在多种药物递送方面已经取得了重大进展,但将治疗性mRNA递送至特定的靶向器官,高效地产生功能性蛋白,依旧是令人兴奋的挑战。
mRNA脂质体纳米粒子是由可电离阳离子脂质、磷脂、胆固醇和聚乙二醇脂质组成,每个组分都在mRNA的高效传递和稳定性中发挥着重要作用。可电离脂质是在低pH值下通过静电作用与带负电荷mRNA结合的关键成分,而且在内吞与内涵体逃逸过程都发挥着重要作用。而内体逃逸环节仍然是影响mRNA转染效率的关键障碍,提高内涵体逃逸效率对于提高mRNA转染具有重要意义。
发明内容
本发明的目的是针对上述存在的问题,提供一种能够将mRNA靶向递送至多种不同器官的中心可降解mRNA脂质体纳米粒子的制备方法与应用。首先合成一种中心可降解的可电离脂质,辅以磷脂,胆固醇与聚乙二醇脂质四组分混合,制备中心可降解脂质体纳米粒子,以极低的剂量,超高的转染效率,将mRNA递送至靶向器官,有望应用于临床治疗;提供该中心可降解的可电离脂质的制备;提供中心可降解脂质体纳米粒子的制备与应用。
本发明的技术方案:
一种中心可降解的可电离脂质,其特征在于由中心可降解氨基核心和疏水尾部组成,其结构式如下所示:
其中:中心可降解氨基核心由线性氨基结构,支化氨基结构或者多氮环类结构与二硫键或缩硫酮结构等刺激响应单元两部分构成;同时,多氮类结构可以作为配位单元与配位金属形成金属配位结构,配位金属为:锌、钙、镁、铝、铁、铜、钆或铕;疏水尾部由线性或支化烷基链组成,主碳原子个数为4-16,支链碳原子个数为0-8,疏水尾部不饱和度为0-6。
一种具有不同器官靶向性中心可降解mRNA脂质体纳米粒子,由中心可降解的可电离脂质、磷脂、胆固醇、聚乙二醇脂质组成;其中:中心可降解的可电离脂质为上述可电离脂质;磷脂为1,2-二油酰-SN-甘油-3-磷酰乙醇胺(DOPE)、1,2-二油酰基-sn-甘油-3-磷酸胆(DOPC)或者二硬脂酰磷脂酰胆碱(DSPC);聚乙二醇脂质为二肉豆蔻酰甘油-聚乙二醇2000(DMG-PEG2000)或者二硬脂酰基磷脂酰乙醇胺-聚乙二醇2000(DSPE-PEG2000),可电离脂质、磷脂、胆固醇、聚乙二醇脂质四组分以15/15/20/1、15/15/25/1、15/15/28/1、15/15/20/1.5、15/15/25/1.5、15/15/28/1.5、15/15/30/1.5或15/15/30/2摩尔比组成。
一种中心可降解的可电离脂质的制备方法,其特征在于包括如下步骤:
1)将响应刺激单元与疏水尾部以摩尔比1:1溶解于溶剂中,在温度为60-80℃下反应12-24h,旋蒸除去溶剂,产物用柱层析纯化,得到含有响应刺激单元的疏水尾部;
2)将中心可降解氨基核心与上述含有响应刺激单元的疏水尾部以摩尔比1:2-6溶解于溶剂中,在温度为50-80℃下反应12-24h,旋蒸除去溶剂,产物用柱层析纯化,得到中心可降解的可电离脂质。
一种具有不同器官靶向性中心可降解mRNA脂质体纳米粒子的制备方法,其特征在于包括如步骤:
1)将摩尔比为15/15/20/1、15/15/25/1、15/15/28/1、15/15/20/1.5、15/15/25/1.5、15/15/28/1.5、15/15/30/1.5或15/15/30/2的中心可降解的可电离脂质、DOPE、胆固醇和DMG-PEG2000用乙醇溶解;
2)将适量mRNA溶解于酸性缓冲液,与上述混合乙醇溶液以3:1,进行混合,制备成纳米粒子溶液;
3)将纳米粒子溶液适用3.5kDa MWCO透析杯在pH=7.4的PBS缓冲液透析2小时,得到粒径为90-150nm的中心可降解mRNA脂质体纳米粒子。
一种具有不同器官靶向性中心可降解mRNA脂质体纳米粒子的应用,其特征在于用于非病毒基因载体,方法如下:
将按照上述方法制备载有mRNA、siRNA或DNA的中心可降解纳米粒子,加入细胞汇合度为70-80%的96孔板,每孔用量5ng,在37℃,5%CO2条件下培养24小时,进行目的基因转染表达。该纳米粒子不仅用于转染常规无限增殖细胞系,还可以转染难转染的细胞系,如干细胞、原代细胞等。
一种具有肝脏靶向中心可降解mRNA脂质体纳米粒子的应用,其特征在于靶向递送mRNA至小鼠肝脏以及相关传感或治疗的应用:
将按照上述方法制备肝脏靶向中心可降解mRNA脂质体纳米粒子,如4A3-SCC-PH,通过尾静脉或内眦静脉注射的方法,以0.025-0.3mg/kg的剂量,注射至小鼠体内,4-12小时后,根据选择的mRNA种类进行传感或者治疗应用。
一种具有脾脏靶向中心可降解mRNA脂质体纳米粒子的应用,其特征在于用于靶向递送mRNA至小鼠次级淋巴系统以及相关传感或治疗的应用,方法如下:
将按照上述方法制备脾脏靶向中心可降解mRNA脂质体纳米粒子,如4A3-SCC-14,通过尾静脉或内眦静脉注射的方法,以0.025-0.3mg/kg的剂量,注射至小鼠体内,4-12小时后,根据选择的mRNA种类进行传感或者治疗应用。
一种具有肺部靶向中心可降解mRNA脂质体纳米粒子的应用,其特征在于用于靶向递送mRNA至小鼠肺部以及相关传感或治疗的应用,方法如下:
将按照上述方法制备肺部靶向中心可降解mRNA脂质体纳米粒子,如9C-SCC-10,通过尾静脉或内眦静脉注射的方法,以0.1-0.3mg/kg的剂量,注射至小鼠体内,4-12小时后,根据选择的mRNA种类进行传感或者治疗应用。
一种具有次级淋巴系统靶向中心可降解mRNA脂质体纳米粒子的应用,其特征在于用于靶向递送mRNA至小鼠次级淋巴系统以及相关传感或治疗的应用,方法如下:
将按照上述方法制备次级淋巴系统中心可降解mRNA脂质体纳米粒子,如4A3-SCC-14,通过尾静脉或内眦静脉注射的方法,以0.025-0.3mg/kg的剂量,注射至小鼠体内,4-12小时后,根据选择的mRNA种类进行传感或者治疗应用。
一种具有血液靶向中心可降解mRNA脂质体纳米粒子的应用其特征在于用于靶向递送mRNA至小鼠血液以及相关传感或治疗的应用,方法如下:
将按照上述方法制备血液靶向中心可降解mRNA脂质体纳米粒子,如9C-SCC-8,通过尾静脉或内眦静脉注射的方法,以0.1-0.3mg/kg的剂量,注射至小鼠体内,4-12小时后,根据选择的mRNA种类进行传感或者治疗应用。
本发明的优点是:
本发明所制备的脂质体纳米粒子,用于非病毒基因载体,可递送mRNA至常规转染常规无限增殖细胞系,还可转染难以转染的干细胞,悬浮细胞或者原代细胞。通过在可电离脂质的氨基核心结构中引入刺激响应基团,有效提升了脂质体纳米粒子在细胞内的内涵体逃逸效率,使mRNA得以释放、表达,展现出极高的转染效率。通过改变氨基核心结构、疏水尾部以及四组分比例,能够实现将mRNA靶向递送至小鼠肝脏,脾脏,肺部,次级淋巴系统、血液以及肿瘤,拓展了脂质体在非病毒基因载体方面的应用。
附图说明
图1为肝脏靶向中心可降解的可电离脂质4A3-SCC-8的核磁谱图。
图2为肺部靶向中心可降解的可电离脂质4A3-SCC-8的核磁谱图。
图3为肝脏靶向的中心可降解Fluc-mRNA脂质体纳米粒子4A3-SCC-8,使用剂量为0.1mg/kg,通过静脉注射在C57BL/6小鼠体内进行转染。
图4为脾脏靶向的中心可降解Fluc-mRNA脂质体纳米粒子2A1-SCC-10,使用剂量为0.1mg/kg,通过静脉注射在C57BL/6小鼠体内进行转染。
图5为肺部靶向的中心可降解Fluc-mRNA脂质体纳米粒子9C-SCC-10,使用剂量为0.1mg/kg,通过静脉注射在C57BL/6小鼠体内进行转染。
图6为次级淋巴系统靶向的中心可降解Fluc-mRNA脂质体纳米粒子4A3-SCC-14,使用剂量为0.1mg/kg,通过静脉注射在C57BL/6小鼠体内进行转染。
图7为血液靶向的中心可降解Fluc-mRNA脂质体纳米粒子Cyc-SCC-10,使用剂量为0.1mg/kg,通过静脉注射在C57BL/6小鼠体内进行转染。
图8为中心可降解Fluc-mRNA脂质体纳米粒子4A3-SCC-8,使用剂量为0.1mg/kg,通过腹腔注射在C57BL/6小鼠体内进行肿瘤检测成像。
具体实施方式
本发明公开了一种具有不同器官靶向性中心可降解mRNA脂质体纳米粒子及其制备方法和应用,中心可降解的可电离脂质由中心可降解氨基核心和疏水尾部组成,其结构式如下所示:
其中:中心可降解氨基核心由线性氨基结构、支化氨基结构或者含氮杂环类结构与二硫键或缩硫酮结构等刺激响应单元两部分构成;同时,含氮杂环类结构可以作为配位单元与配位金属形成金属配位结构,配位金属为:锌、钙、镁、铝、铁、铜、钆或铕;疏水尾部由线性或支化烷基链组成,主碳原子个数为4-16,支链碳原子个数为0-8,疏水尾部不饱和度为0-6。
以下结合具体实施例对本发明方案作进一步说明但这些实施例仅用于说明本发明而不用于限制本发明的范围,如实施例中仅涉及锌、铝等配位金属,对所未涉及的技术特征组成的技术方案,虽未逐一给出实施例,但其与下述实施例具有相同的技术效果。另外进一步有必要指出,本领域技术人员可以对本发明做各种修改或改动,这些等价形式同样落于本申请所附权利要求书所限定的范围。
实施例1:
一种具有肝脏靶向的中心可降解mRNA脂质体纳米粒子,由中心可降解的可电离脂质4A3-SCC-8、DOPE、Chol、DSPE-PEG2000四组分,以15/15/20/1的摩尔比组成,4A3-SCC-8结构式如下所示:
一种所述中心可降解的可电离脂质4A3-SCC-8制备方法,包括如下步骤:
1)将二硫键响应刺激单元SS与辛硫醇以摩尔比1:1溶解于溶剂DMSO中,在温度为80℃下反应24h,除去溶剂,产物用柱层析纯化,得到含有响应刺激单元的疏水尾部SCC-8;
2)将氨基结构N'N-双(3-氨丙基)甲胺与上述含有响应刺激单元的疏水尾部SCC-8以摩尔比1:4溶解于溶剂DMSO中,在温度为80℃下反应24h,除去溶剂,产物用柱层析纯化,得到中心可降解的可电离脂质4A3-SCC-8。
4A3-SCC-8肝脏靶向的中心可降解mRNA脂质体纳米粒子的制备方法,包括如下步骤:
1)将摩尔比为15/15/25/1、15/15/25/1.5、15/15/20/1、15/15/20/1.5的4A3-SCC-8、DOPE、胆固醇和DSPE-PEG2000用乙醇溶解;
2)将适量mRNA溶解于酸性缓冲液,与上述混合乙醇溶液以3:1,进行混合,制备成纳米粒子溶液;
3)将纳米粒子溶液适用3.5kDa MWCO透析杯在pH=7.4的PBS缓冲液透析2小时,得到中心可降解mRNA脂质体纳米粒子4A3-SCC-8。
图1为肝脏靶向中心可降解的可电离脂质4A3-SCC-8的核磁谱图。
实施例2:
一种具有肺部靶向的中心可降解mRNA脂质体纳米粒子,由中心可降解的可电离脂质9C-SCC-10、DSPC、Chol、DMG-PEG2000四组分,以15/15/25/1、15/15/25/1.5、15/15/20/1、15/15/20/1.5摩尔比组成,9C-SCC-10结构式如下所示:
一种所述中心可降解的可电离脂质9C-SCC-10制备方法,包括如下步骤:
1)将二硫键响应刺激单元SS与癸硫醇以摩尔比1:1溶解于溶剂DMSO中,在温度为70℃下反应24h,除去溶剂,产物用柱层析纯化,得到含有响应刺激单元的疏水尾部SCC-10;
2)将氨基结构1,4,7-三氮杂环壬烷与上述含有响应刺激单元的疏水尾部SCC-10以摩尔比1:3溶解于溶剂DMSO中,在温度为70℃下反应24h,除去溶剂,柱层析纯化得到产物中心可降解的可电离脂质9C-SCC-10;
3)将9C-SCC-10溶于适量溶剂,加入等当量配位金属化合物硝酸锌溶解,60℃搅拌12h,旋蒸去溶解,得到产物Zn-SCC-10。
Zn-SCC-10肺部靶向的中心可降解Fluc-mRNA脂质体纳米粒子的制备方法,包括如下步骤:
1)将摩尔比为15/15/25/1.5、15/15/28/1.5、15/15/30/1.5、15/15/30/2的9C-SCC-10、DSPC、胆固醇和DMG-PEG2000用乙醇溶解;
2)将适量mRNA溶解于酸性缓冲液,与上述混合乙醇溶液以3:1,进行混合,制备成纳米粒子溶液;
3)将纳米粒子溶液适用3.5kDa MWCO透析杯在pH=7.4的PBS缓冲液透析2小时,得到中心可降解mRNA脂质体纳米粒子Zn-SCC-10。
图2为肺部靶向中心可降解的可电离脂质4A3-SCC-8的核磁谱图。
实施例3:
4A3-SCC-8肝脏靶向的中心可降解mRNA脂质体纳米粒子的体内应用;
1)将4A3-SCC-8肝脏靶向的中心可降解Fluc-mRNA脂质体纳米粒子通过尾静脉注入C57BL/6小鼠体内,4A3-SCC-8用量为0.1mg/kg;
2)6h小时后,腹腔注射40mg/ml D-荧光素溶液100微升;通过小动物活体成像仪进行成像测试;取出小鼠心脏、肝脏、脾脏、肺部、肾脏,进行主要器官成像测试。
图3为肝脏靶向的中心可降解Fluc-mRNA脂质体纳米粒子4A3-SCC-8,使用剂量为0.1mg/kg,通过静脉注射在C57BL/6小鼠体内进行成像。
实施例4:
2A1-SCC-10脾脏靶向的中心可降解mRNA脂质体纳米粒子的体内应用;
1)将2A1-SCC-10肺部靶向的中心可降解Fluc-mRNA脂质体纳米粒子通过尾静脉注入C57BL/6小鼠体内,2A1-SCC-10用量为0.1mg/kg;
2)6h小时后,腹腔注射40mg/ml D-荧光素溶液100微升;通过小动物活体成像仪进行成像测试;取出小鼠心脏、肝脏、脾脏、肺部、肾脏,进行主要器官成像测试。
图4为脾脏靶向的中心可降解Fluc-mRNA脂质体纳米粒子2A1-SCC-10,使用剂量为0.1mg/kg,通过静脉注射在C57BL/6小鼠体内进行成像。
实施例5:
Zn-SCC-10肺部靶向的中心可降解mRNA脂质体纳米粒子的体内应用;
1)将Zn-SCC-10肺部靶向的中心可降解Fluc-mRNA脂质体纳米粒子通过尾静脉注入C57BL/6小鼠体内,9C-SCC-10用量为0.1mg/kg;
2)6h小时后,腹腔注射40mg/ml D-荧光素溶液100微升;通过小动物活体成像仪进行成像测试;取出小鼠心脏、肝脏、脾脏、肺部、肾脏,进行主要器官成像测试。
图5为肺部靶向的中心可降解Fluc-mRNA脂质体纳米粒子Zn-SCC-10,使用剂量为0.1mg/kg,通过静脉注射在C57BL/6小鼠体内进行成像。
实施例6:
4A3-SCC-14次级淋巴系统靶向的中心可降解mRNA脂质体纳米粒子的体内应用;
1)将4A3-SCC-14次级淋巴系统靶向的中心可降解Fluc-mRNA脂质体纳米粒子通过尾静脉注入C57BL/6小鼠体内,4A3-SCC-14用量为0.1mg/kg;
2)6h小时后,腹腔注射40mg/ml D-荧光素溶液100微升;通过小动物活体成像仪进行成像测试;取出小鼠心脏、肝脏、脾脏、肺部、肾脏,进行主要器官成像测试。
图6为次级淋巴系统的中心可降解Fluc-mRNA脂质体纳米粒子4A3-SCC-14,使用剂量为0.1mg/kg,通过静脉注射在C57BL/6小鼠体内进行成像。
实施例7:
Cyc-SCC-10血液靶向的中心可降解mRNA脂质体纳米粒子的体内应用;
1)将Cyc-SCC-10血液靶向的中心可降解Fluc-mRNA脂质体纳米粒子通过尾静脉注入C57BL/6小鼠体内,Cyc-SCC-10用量为0.1mg/kg;
2)6h小时后,腹腔注射40mg/ml D-荧光素溶液100微升;通过小动物活体成像仪进行成像测试;取出小鼠心脏、肝脏、脾脏、肺部、肾脏,进行主要器官成像测试。mRNA次级淋巴系统递送实验:
图7为血液系统的中心可降解Fluc-mRNA脂质体纳米粒子Cyc-SCC-10,使用剂量为0.1mg/kg,通过静脉注射在C57BL/6小鼠体内进行成像。
实施例8:
中心可降解mRNA脂质体纳米粒子4A3-SCC-8的小鼠深度肿瘤检测应用;
1)将4A3-SCC-8中心可降解Fluc-mRNA脂质体纳米粒子4A3-SCC-8通过腹腔注射注入C57BL/6小鼠体内,4A3-SCC-8用量为0.1mg/kg;
2)6h小时后,腹腔注射40mg/ml D-荧光素溶液100微升;通过小动物活体成像仪进行成像测试;
图8为血液系统的中心可降解Fluc-mRNA脂质体纳米粒子Cyc-SCC-10,使用剂量为0.1mg/kg,通过静脉注射在C57BL/6小鼠体内进行成像。
实施例9:
所制备4A3-SCC-8脂质体纳米粒子的应用,用于非病毒基因载体,递送mRNA至常规转染常规无限增殖细胞系,还可转染难以转染的干细胞,悬浮细胞或者原代细胞。
4A3-SCC-8脂质体纳米粒子体外细胞转染实验与细胞毒性实验:
将按照上述方法制备的4A3-SCC-8脂质体纳米粒子加入至每孔细胞数为1×104的96孔培养板,mRNA的用量为20ng/孔,5%CO2细胞培养箱,37℃孵育12h,使用ONE-Glo+Tox荧光素酶检测试剂盒评估转染效率与细胞毒性。
Claims (10)
2.一种中心可降解mRNA脂质体纳米粒子,其特征在于由中心可降解的可电离脂质、磷脂、胆固醇、聚乙二醇脂质组成,其中:中心可降解的可电离脂质为权利要求1中所述的可电离脂质;磷脂为1,2-二油酰-SN-甘油-3-磷酰乙醇胺(DOPE)、1,2-二油酰基-sn-甘油-3-磷酸胆(DOPC)或者二硬脂酰磷脂酰胆碱(DSPC);聚乙二醇脂质为二肉豆蔻酰甘油-聚乙二醇2000(DMG-PEG2000)或者二硬脂酰基磷脂酰乙醇胺-聚乙二醇2000(DSPE-PEG2000),可电离脂质、磷脂、胆固醇、聚乙二醇脂质四组分以15/15/20/1、15/15/25/1、15/15/28/1、15/15/20/1.5、15/15/25/1.5、15/15/28/1.5、15/15/30/1.5或15/15/30/2摩尔比组成。
3.一种权利要求1所述的中心可降解的可电离脂质的制备方法,其特征在于包括如下步骤:
1)将响应刺激单元与疏水尾部以摩尔比1:1溶解于溶剂中,在温度为60-80℃下反应12-24h,旋蒸除去溶剂,产物用柱层析纯化,得到含有响应刺激单元的疏水尾部;
2)将中心可降解氨基核心与上述含有响应刺激单元的疏水尾部以摩尔比1:2-6溶解于溶剂中,在温度为50-80℃下反应12-24h,旋蒸除去溶剂,产物用柱层析纯化,得到中心可降解的可电离脂质。
4.一种权利要求2所述的中心可降解mRNA脂质体纳米粒子的制备方法,其特征在于包括如步骤:
1)将摩尔比为15/15/20/1、15/15/25/1、15/15/28/1、15/15/20/1.5、15/15/25/1.5、15/15/28/1.5、15/15/30/1.5或15/15/30/2的中心可降解的可电离脂质、DOPE、胆固醇和DMG-PEG2000用乙醇溶解;
2)将适量mRNA溶解于酸性缓冲液,与上述混合乙醇溶液以3:1,进行混合,制备成纳米粒子溶液;
3)将纳米粒子溶液适用3.5kDaMWCO透析杯在pH=7.4的PBS缓冲液透析2小时,得到粒径为90-150nm的中心可降解mRNA脂质体纳米粒子。
5.一种权利要求2所述的中心可降解mRNA脂质体纳米粒子的应用,其特征在于用于非病毒基因载体,方法如下:
将按照权利要求2方法制备,载有mRNA、siRNA或DNA的中心可降解纳米粒子,加入细胞汇合度为70-80%的96孔板,每孔用量5ng,在37℃,5%CO2条件下培养24小时,进行目的基因转染表达;该纳米粒子用于转染常规无限增殖细胞系,或用于转染难转染的细胞系。
6.一种权利要求2所述的中心可降解mRNA脂质体纳米粒子的应用,其特征在于用于靶向递送mRNA至小鼠肝脏以及相关传感或治疗载体,方法如下:
将按照权利要求2方法制备肝脏靶向中心可降解mRNA脂质体纳米粒子4A3-SCC-PH,通过尾静脉或内眦静脉注射的方法,以0.025-0.3mg/kg的剂量,注射至小鼠体内,4-12小时后,根据选择的mRNA种类进行传感应用。
7.一种权利要求2所述的中心可降解mRNA脂质体纳米粒子的应用,其特征在于用于靶向递送mRNA至小鼠脾脏以及相关传感或治疗载体,方法如下:
将按照权利要求2方法制备脾脏靶向中心可降解mRNA脂质体纳米粒子2A1-SCC-10,通过尾静脉或内眦静脉注射的方法,以0.025-0.3mg/kg的剂量,注射至小鼠体内,4-12小时后,根据选择的mRNA种类进行传感应用。
8.一种权利要求2所述的中心可降解mRNA脂质体纳米粒子的应用,其特征在于用于靶向递送mRNA至小鼠肺部以及相关传感或治疗载体,方法如下:
将按照权利要求2方法制备肺部靶向中心可降解mRNA脂质体纳米粒子9C-SCC-10,通过尾静脉或内眦静脉注射的方法,以0.1-0.3mg/kg的剂量,注射至小鼠体内,4-12小时后,根据选择的mRNA种类进行传感应用。
9.一种权利要求2所述的中心可降解mRNA脂质体纳米粒子的应用,其特征在于用于靶向递送mRNA至小鼠次级淋巴系统靶向以及相关传感或治疗载体,方法如下:
将按照权利要求2方法制备次级淋巴系统靶向中心可降解mRNA脂质体纳米粒子9C-SCC-8,通过尾静脉或内眦静脉注射的方法,以0.1-0.3mg/kg的剂量,注射至小鼠体内,4-12小时后,根据选择的mRNA种类进行传感应用。
10.一种权利要求2所述的中心可降解mRNA脂质体纳米粒子的应用,其特征在于用于靶向递送mRNA至小鼠血液以及相关传感或治疗载体,方法如下:
将按照权利要求2方法制备血液靶向中心可降解mRNA脂质体纳米粒子9C-SCC-8,通过尾静脉或内眦静脉注射的方法,以0.1-0.3mg/kg的剂量,注射至小鼠体内,4-12小时后,根据选择的mRNA种类进行传感应用。
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