CN110755635B - Flu@α-cd47@RGD制剂的合成方法 - Google Patents

Flu@α-cd47@RGD制剂的合成方法 Download PDF

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CN110755635B
CN110755635B CN201911114050.1A CN201911114050A CN110755635B CN 110755635 B CN110755635 B CN 110755635B CN 201911114050 A CN201911114050 A CN 201911114050A CN 110755635 B CN110755635 B CN 110755635B
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郑斌
王树超
明东
李晓红
刘爽
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Abstract

本发明涉及Flu@α‑cd47@RGD制剂的合成方法，具体为一种通过策略仿生模拟成功合成Flu@α‑cd47@RGD肿瘤联合治疗纳米制剂的方法。主要步骤为两步复乳液法合成Flu@α‑cd47@RGD纳米颗粒。RGD靶向分子帮助高效靶向肿瘤病灶；流感病毒利用强烈免疫激活功能来活化全身免疫系统，引起免疫应答；CD47抗体屏蔽肿瘤表面的免疫细胞抑制分子，防止肿瘤免疫逃逸。

Description

Flu@α-cd47@RGD制剂的合成方法
技术领域
本发明涉及一种通过蛋白介导仿生模拟策略成功制备出的Flu@α-cd47@RGD纳米诊疗剂，具体涉及一种Flu@α-cd47@RGD肿瘤联合治疗纳米制剂的合成方法。
背景技术
目前，肿瘤是世界上对人类威胁最大的疾病之一。免疫治疗通过激活人体免疫系统，依靠自身免疫机能杀灭癌细胞和肿瘤组织，从而达到治疗癌症的作用。因此，免疫治疗是治疗肿瘤最有效的方法之一。
流感病毒作为异物在体内可以激发全身免疫系统产生细胞因子风暴(如干扰素、肿瘤坏死因子和各种白细胞介素等)，并使在抗肿瘤治疗过程中具有重要作用的树突状细胞(DC细胞，提呈肿瘤抗原)，巨噬细胞(
Figure BDA0002273565070000011
细胞，吞噬肿瘤细胞)和自然杀伤细胞(NK细胞，杀伤肿瘤细胞)等被大量激活，随后大幅提高T细胞的增值效率。这种基于流感病毒的复合纳米制剂可全身性激活机体免疫功能，给肿瘤造成全方位的杀伤和清除，相对于传统肿瘤治疗方法，该策略使肿瘤治疗更加高效。
RGD靶向分子是一类含有精氨酸-甘氨酸-天冬氨酸的短肽，可介导肿瘤的靶向治疗。抗肿瘤药物及其递送系统经过RGD靶向分子的修饰可増加药物的肿瘤主动靶向特性，达到更有效、精确和安全的治疗。
发病状态下，肿瘤细胞可逃避机体的免疫监视，导致肿瘤发展与转移。而蛋白CD47作为一种敌我鉴别信号分子，与肿瘤细胞逃避免疫吞噬密切相关。利用蛋白CD47抗体屏蔽肿瘤表面的免疫细胞抑制分子防止肿瘤免疫逃逸，将是非常有效的肿瘤免疫治疗新途径。
制备出的该药物有有以下几大优点：1)RGD靶向分子可以帮助高效靶向肿瘤病灶；2)流感病毒可以利用强烈免疫激活功能来活化全身免疫系统，引起免疫应答；3)α-cd47抗体屏蔽肿瘤表面的免疫细胞抑制分子，可以有效防止肿瘤免疫逃逸；
发明内容
本发明涉及一种策略仿生模拟成功合成Flu@αcd47@RGD肿瘤联合治疗纳米制剂的合成方法。
本发明的技术方案是Flu@α-cd47@RGD肿瘤联合治疗纳米制剂的合成方法，包括如下步骤：
(1)利用两步复乳液法合成Flu@α-cd47@RGD纳米颗粒的方法如下：
1)将1-3mg RGD溶于10ml二氯甲烷中作为油相(O)，以5-15ml 0.01mg/ml Flu病毒溶液和1-3ml 0.01mg/mlα-cd47抗体复合物溶液作为内水相(W1)。
2)将W1加入到O中60W超声1min，形成油包水(W1/O)型乳液。
3)将W1/O加入1.5％PVA水溶液中100W超声7min，得到水包油包水(W1/O/W2)型复乳液。
本发明的优势在于：1)RGD靶向分子可以帮助高效靶向肿瘤病灶；2)流感病毒可以利用强烈免疫激活功能来活化全身免疫系统，引起免疫应答；3)α-cd47抗体屏蔽肿瘤表面的免疫细胞抑制分子，可以有效防止肿瘤免疫逃逸。
附图说明
图1：Flu@α-cd47@RGD纳米颗粒粒径分布；
图2：Flu@α-cd47@RGD纳米颗粒粒径相关函数。
具体实施方式
实施例1：
Flu@α-cd47@RGD肿瘤联合治疗纳米制剂的合成方法，具体步骤如下：
(1)利用两步复乳液法合成Flu@α-cd47@RGD纳米颗粒的方法如下：
1)将1mg RGD溶于10ml二氯甲烷中作为油相(O)，以5ml 0.01mg/ml Flu病毒溶液和1ml 0.01mg/mlα-cd47抗体复合物溶液作为内水相(W1)。
2)将W1加入到O中60W超声1min，形成油包水(W1/O)型乳液。
3)将W1/O加入1.5％PVA水溶液中100W超声7min，得到水包油包水(W1/O/W2)型复乳液。
实施例2：
Flu@α-cd47@RGD肿瘤联合治疗纳米制剂的合成方法，具体步骤如下：
(1)利用两步复乳液法合成Flu@α-cd47@RGD纳米颗粒的方法如下：
1)将2mg RGD溶于10ml二氯甲烷中作为油相(O)，以10ml 0.01mg/ml Flu病毒溶液和2ml 0.01mg/mlα-cd47抗体复合物溶液作为内水相(W1)。
2)将W1加入到O中60W超声1min，形成油包水(W1/O)型乳液。
3)将W1/O加入1.5％PVA水溶液中100W超声7min，得到水包油包水(W1/O/W2)型复乳液。
实施例3：
Flu@α-cd47@RGD肿瘤联合治疗纳米制剂的合成方法，具体步骤如下：
(1)利用两步复乳液法合成Flu@α-cd47@RGD纳米颗粒的方法如下：
1)将3mg RGD溶于10ml二氯甲烷中作为油相(O)，以15ml 0.01mg/ml Flu病毒溶液和3ml 0.01mg/mlα-cd47抗体复合物溶液作为内水相(W1)。
2)将W1加入到O中60W超声1min，形成油包水(W1/O)型乳液。
3)将W1/O加入1.5％PVA水溶液中100W超声7min，得到水包油包水(W1/O/W2)型复乳液。

Claims (1)

1.Flu@α-cd47@RGD制剂的合成方法，其特征是，包括如下步骤：
(1)利用两步复乳液法合成Flu@α-cd47@RGD纳米颗粒的方法如下：
1)将1-3mg RGD溶于10ml二氯甲烷中作为油相(O)，以5-15ml 0.01mg/ml Flu病毒溶液和1-3ml 0.01mg/mlα-cd47抗体复合物溶液作为内水相(W1)；
2)将W1加入到O中60W超声1min，形成油包水(W1/O)型乳液；
3)将W1/O加入1.5％PVA水溶液中100W超声7min，得到水包油包水(W1/O/W2)型复乳液。
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