CN113980671A - 多胺衍生物修饰的量子点、制备方法和作为纳米药物载体的应用 - Google Patents
多胺衍生物修饰的量子点、制备方法和作为纳米药物载体的应用 Download PDFInfo
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- CN113980671A CN113980671A CN202111330835.XA CN202111330835A CN113980671A CN 113980671 A CN113980671 A CN 113980671A CN 202111330835 A CN202111330835 A CN 202111330835A CN 113980671 A CN113980671 A CN 113980671A
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Abstract
本发明是属于药物化学领域,具体涉及多胺衍生物修饰的量子点的制备方法和作为纳米药物载体的应用,该多胺衍生物修饰的量子点纳米药物载体具有下式所示结构:
Description
技术领域
本发明属于药物化学技术领域,具体涉及一种多胺衍生物修饰的量子点、制备方法和其作为纳米药物载体的应用。
背景技术
量子点是一类由Ⅱ-Ⅵ族及Ⅲ-Ⅴ族元素构成的、尺寸在2-100nm的半导体纳米晶体。与传统的有机染料相比,该类材料具有独特的光化学和光物理性能,主要体现在激发光谱宽、发射光谱窄、荧光寿命长及抗漂白能力强等。更重要的是,量子点发射光谱的颜色能够随其尺寸的改变而变化,使其能够广泛用于荧光成像、药物追踪及多色标记等。但是,目前合成的大部分量子点都含有镉、铅等重金属元素,对生物体具有一定的毒副作用,只有通过对量子点的表面进行修饰,才能将其用于生物医药领域。所以,通过对量子点进行修饰进而得到水溶性好的量子点是目前的一个研究方向。
多胺是指一类广泛存在于动植物体内的、含有三个及其以上氮原子的有机小分子,该类化合物包括精胺(spermine)、亚精胺(spermidine)、腐胺(putrescine)及尸胺(cadaverine)等。研究表明,该类化合物对细胞的生长、增殖等具有较大影响,也可以作为标志物应用于疾病诊断。多胺化合物一般带正电荷,同时由于分子内伯、仲及叔胺的存在,其用于修饰半导体材料后,能够增加半导体材料表面的反应位点,同时也会增加半导体材料的水溶性及生物活性等。
氨基酸是一类是含有碱性氨基和酸性羧基的有机化合物。氨基酸在人体内通过代谢可以发挥下列一些作用:①合成组织蛋白质;②变成酸、激素、抗体、肌酸等含氨物质;③转变为碳水化合物和脂肪;④氧化成二氧化碳和水及尿素,产生能量。由多种氨基酸组成的复方制剂在现代静脉营养输液以及“要素饮食”疗法中占有非常重要的地位,对维持危重病人的营养,抢救患者生命起积极作用,成为现代医疗中不可少的医药品种之一。
10-羟基喜树碱(10-HCPT)是一类从喜树中提取到的抗肿瘤活性药,其主要是通过抑制拓扑异构酶I的活性而发挥作用。但是,该类化合物存在水溶性不好、见光易分解等缺点,使其应用受到限制。因此,根据多胺、氨基酸及量子点的作用特点,设计合成多胺衍生物修饰的量子点,希望达到靶向给药目的,从而实现抗肿瘤的靶向作用。
发明内容
本发明目的在于克服现有技术缺陷,提供一种多胺衍生物修饰的量子点、制备方法和其作为纳米药物载体的应用。
为实现上述目的,本发明采用如下技术方案:
一种多胺衍生物修饰的量子点,其具有如下结构:
式中,R为氨基酸残基,QDs指量子点CdSe。
进一步的,所述氨基酸为苯丙氨酸、色氨酸或半胱氨酸等。
本发明提供了上述多胺衍生物修饰的量子点的制备方法,其合成路线如下所示:
具体包括如下步骤:
1)将邻苯二甲酰亚胺a溶于无水乙醇中,加入含氢氧化钾(KOH)的无水乙醇溶液,析出的固体经干燥得邻苯二甲酰亚胺钾盐;然后和1,3二溴丙烷在有机溶剂丙酮中回流反应8-20h,冷却,经过滤、减压蒸馏和重结晶得到化合物b;
2)将Boc保护的丙二胺溶于乙腈中,加入碱性碳酸物和化合物b于30-60℃反应8-20h,经后处理得到化合物c;
3)将化合物c溶于甲醇中,加入二碳酸二叔丁酯(BOC)2O后于室温反应8-20h,经后处理得到化合物d;
4)将化合物d溶于乙醇中,加入水合肼后于室温反应8-20h,反应结束经后处理得到化合物e;
5)将化合物e溶于乙腈中,加入碱性碳酸物和化合物b于30-60℃反应8-20h,经后处理得到化合物f;
6)将化合物f溶于甲醇中,加入二碳酸二叔丁酯后于室温反应8-20h,经后处理得到化合物g;
7)将化合物g溶于乙醇中,加入水合肼后于室温反应8-20h,反应结束经后处理得到化合物h;
8)以氨基酸i为原料,加入二碳酸二叔丁酯后于室温反应8-20h,经后处理得到氨基保护的氨基酸化合物j;
9)将化合物j溶于无水乙腈中,在1,2-二氯乙烷和N-羟基丁二酰亚胺作用下与化合物h于室温反应8-20h,经分离纯化得到多胺衍生物k;
10)将多胺衍生物k加入到CdSe量子点的氯仿溶液中,同时加入三乙胺,室温超声至量子点完全由有机层转入到上层水相中,加入适量乙酸乙酯震荡使产生沉淀,经离心、洗涤得到的沉淀物即为多胺衍生物修饰的量子点l。
进一步的,步骤1)中所述邻苯二甲酰亚胺和氢氧化钾的摩尔比可以为1:2-4;步骤2)中所述碱性碳酸物为K2CO3或Na2CO3,碱性碳酸物的用量以调节溶液pH为8-10为准;化合物b和Boc保护的丙二胺的摩尔比可以为1:1-2。
进一步的,步骤3)中所述化合物c与二碳酸二叔丁酯的摩尔比可以为1:2-4;步骤4)中所述化合物d和水合肼的摩尔比可以为1:10-20。
进一步的,步骤5)中所述碱性碳酸物为K2CO3或Na2CO3,碱性碳酸物的用量以调节溶液pH为8-10为准;化合物b和化合物e的摩尔比可以为1:1-2。
进一步的,步骤6)中所述化合物f和二碳酸二叔丁酯的摩尔比可以为1:1-3;步骤7)中所述化合物g和水合肼的摩尔比可以为1:10-20。
进一步的,步骤9)中所述化合物h与化合物j的摩尔比可以为1:1-2;步骤10)中量子点与多胺衍生物k的摩尔比可以为1:6-7。
本发明还提供了上述多胺衍生物修饰的量子点作为纳米药物载体在载药方面的应用。
本发明还提供了上述多胺衍生物修饰的量子点作为纳米药物载体在细胞生物活性方面的应用。
本发明多胺衍生物修饰的量子点是通过多胺衍生物在碱性环境下与量子点在氯仿溶剂中反应,经过沉淀、离心分离提纯得到多胺衍生物修饰的量子点。和现有技术相比,本发明的有益效果如下:
1)本发明是基于多胺的结构,合成了一类多胺衍生物修饰的量子点纳米粒子。把氨基酸和多胺结合在一起来修饰量子点,可以改善量子点的水溶性,稳定性和生物相容性,制成生物相容性高的纳米材料,实现其在药物化学领域中作为纳米药物载体的作用;
2)本发明提供了该多胺衍生物修饰的量子点纳米粒子简单易行的制备方法,其具有反应操作条件温和,工艺流程短、能耗低,投资少,成本低、纯度较高等优点;
3)本发明多胺衍生物修饰的量子点纳米药物载体具有很好的光学特征,可以为药物的运载和释放提供较好的光学信号,为药物的示踪提供便利条件,至今鲜有报道。
附图说明
图1是本发明实施例1产品(A)量子点(CdSe)、(B)多胺衍生物修饰的量子点l(CdSe@Polyamine,纳米药物载体)和(C)载药后的产物m(CdSe@Polyamine-cHCPT)的透射电镜图谱;
图2是本发明实施例1产品量子点(CdSe)、10-羟基喜树碱(10-HCPT)、多胺衍生物修饰的量子点l(CdSe@Polyamine,纳米药物载体)和载药后的产物m(CdSe@Polyamine-cHCPT)的紫外吸收光谱;
图3是本发明实施例1产品量子点(CdSe)、10-羟基喜树碱(10-HCPT)、多胺衍生物修饰的量子点l(CdSe@Polyamine,纳米药物载体)和载药后的产物m(CdSe@Polyamine-cHCPT)的荧光光谱。
具体实施方式
以下结合实施例对本发明的技术方案作进一步地详细介绍,但本发明的保护范围并不局限于此。
实验仪器名称与型号:
日本JEOL JEM-200CX透射电子显微镜;
美国Perkin-Elmer Lambda-850紫外分光光度计;
美国Perkin-Elmer Ls55荧光分光光度计;
美国BioTek多功能酶标仪;
本发明中,如无特殊说明,室温指代25±5℃。
下述实施例中,所用量子点CdSe采用本领域常规技术制备即可,本发明不再赘述。
实施例1
制备R为半胱氨酸残基时,多胺衍生物修饰的量子点纳米药物载体的合成步骤:
1)制备化合物b:在250mL圆底烧瓶中加入7.94g(0.054mol)邻苯二甲酰亚胺a和200mL无水乙醇,加热回流至固体完全溶解,将热溶液倒入含有KOH 6.72g(0.12mol)的无水乙醇溶液中,立即有白色晶体析出,抽滤、干燥得到邻苯二甲酰亚胺钾盐;然后在250mL圆底烧瓶中先后加入90.95g(0.45mol)1,3二溴丙烷和100mL丙酮,搅拌条件下分批加入27.75g(0.15mol)邻苯二甲酰亚胺钾盐,搅拌回流12h,冷却。过滤除去反应生成的KBr,减压蒸馏除去丙酮和过量的1,3二溴丙烷,剩余固体用无水乙醇重结晶,得到白色固体b;
2)制备化合物c:将Boc保护的丙二胺(14mmol)溶于30mL乙腈中,加无水碳酸钾4.14g(30mmol)以调节溶液pH为9,室温搅拌15min,升温到45℃,分三批加入化合物b14mmol,控温45℃,反应过夜(12h)。减压蒸除乙腈,残余物用30mL氯仿提取,3×40mL 10%的Na2CO3水溶液洗涤,收集有机层,有机层用无水硫酸钠干燥,减压蒸除氯仿,得淡黄色油状物(含杂质)c;
3)制备化合物d:将获得的油状物c(10mmol)溶于50mL的甲醇溶剂中,加入(BOC)2O4.36g(20mmol),室温搅拌反应过夜。减压蒸除溶剂,残余物用40mL氯仿提取,3×40mL水洗涤,收集有机层,有机层用无水硫酸钠干燥,减压蒸除氯仿,硅胶柱分离(石油醚和乙酸乙酯体积比1:1洗脱)提纯得淡黄色油状化合物d;
4)制备化合物e:将化合物d(5mmol)溶于30mL乙醇中,加水合肼2.5mL(50mmol),室温搅拌过夜至有大量白色不溶性固体出现,减压蒸除溶剂,残渣溶于30mL氯仿中,3×30mL10%的Na2CO3水溶液洗涤,收集有机层,有机层用无水硫酸钠干燥,减压蒸除氯仿,得淡黄色油状化合物e;
5)制备化合物f:将化合物e(5mmol)溶于30mL乙腈中,加无水碳酸钾0.55g(4mmol)以调节溶液pH为9,室温搅拌15min,升温到45℃,分三批分别加入化合物b 2.5mmol,控温45℃,反应过夜。减压蒸除乙腈,残余物用30mL氯仿提取,3×30mL 10%的Na2CO3水溶液洗涤,收集有机层,有机层用无水硫酸钠干燥,减压蒸除氯仿,得淡黄色油状物f;
6)制备化合物g:将油状物f(2.5mmol)溶于50mL的甲醇溶剂中,加入(BOC)2O5mmol,室温搅拌过夜,TLC监测。减压蒸除溶剂,残余物用40mL氯仿提取,3×40mL水洗涤,收集有机层,有机层用无水硫酸钠干燥,减压蒸除氯仿,硅胶柱分离(石油醚和乙酸乙酯体积比1:1洗脱)提纯得淡黄色油状化合物g;
7)制备化合物h:将化合物g(2.5mmol)溶于30mL乙醇中,加水合肼1.2mL(25mmol),室温搅拌过夜至有大量白色不溶性固体出现,减压蒸除溶剂,残渣溶于30mL氯仿中,3×30mL10%的Na2CO3水溶液洗涤,收集有机层,有机层用无水硫酸钠干燥,减压蒸除氯仿,得淡黄色或无色油状化合物h;
8)制备化合物j:将半胱氨酸i(2.5mmol)溶于50mL的甲醇溶剂中,加入(BOC)2O5mmol,室温搅拌过夜,TLC监测。减压蒸除溶剂,残余物用40mL氯仿提取,3×40mL水洗涤,收集有机层,有机层用无水硫酸钠干燥,减压蒸除氯仿,硅胶柱分离(石油醚和乙酸乙酯体积比1:1洗脱)提纯得淡黄色化合物j。
9)制备化合物k:取1.11g(5mmol)化合物j溶于15mL的无水乙腈中,搅拌溶解,向其中加入0.96g 1,2-二氯乙烷(EDC)(5mmol)和0.58g N-羟基丁二酰亚胺(NHS)(5mmol),继续搅拌2h,向其中加入5mmol化合物h,室温搅拌反应过夜,蒸干溶剂,向其中加入10mL CH2Cl2溶解油状物,并用10%Na2CO3水溶液洗涤、收集并蒸干有机层溶剂,得混浊的油状化合物。然后向其中加入5mL蒸馏水,并用CH2Cl2洗涤,收集并真空蒸干水层,得白色的固体化合物k;
10)制备化合物l:取化合物k(6mmol)溶于1mL蒸馏水中,加入到1mL含1mmol CdSe量子点的氯仿溶液中,同时加入10滴三乙胺,室温超声4h,直到量子点完全由有机层转入到上层水相中,向其中加入适量的(5mL)乙酸乙酯震荡使其产生沉淀,离心除去上清液,并用乙酸乙酯多次洗涤,得干净的沉淀物,即为多胺衍生物修饰的量子点l(QDs@Polyamine);
11)制备化合物m:向含有10mL无水二甲亚砜的圆底烧瓶中加入0.208g(0.58mmol)10-羟基喜树碱、0.14g(1.16mmol)4-二甲氨基吡啶和93.0mg(0.93mmol)丁二酸酐,室温避光搅拌0.5h,然后再向其中加入15.6mg(0.156mmol)丁二酸酐,继续搅拌12h。反应到时间后,向其中加入1.5mL 20%的甲醇溶液,继续搅拌0.5h,使反应体系中多余的丁二酸酐水解掉,然后在低于40℃的条件下蒸干溶剂。向黄色油状物中加入10.0mL 50%的甲醇溶液,超声至溶液变为浑浊,4℃条件下静置5h,离心得黄色化合物,将其溶于2mL的DMSO中,向其中加入EDC(91mg,0.47mmol)和NHS(55.0mg,0.47mmol),然后向其中加入(0.5mmol)上述制备好的多胺衍生物修饰的量子点l,继续搅拌4h,离心并洗涤沉淀,得红色固体m(QDs@Polyamine-cHCPT)。
利用透射电镜对量子点(CdSe)及多胺衍生物修饰后的量子点l(CdSe@Polyamine)和载药后的产物m(CdSe@Polyamine-cHCPT)的大小、分散程度进行表征,结果见图1。图1可以看出:多胺衍生物修饰后的量子点l在水中均分散均匀,呈球形,多胺衍生物修饰的量子点作为纳米药物载体负载cHCPT后粒径由~5nm增加到~6nm。
利用紫外吸收光谱对量子点(CdSe)及多胺衍生物修饰后的量子点l(CdSe@Polyamine)和载药后的产物m(CdSe@Polyamine-cHCPT)进行表征,结果见图2。图2可以看出:多胺衍生物修饰后的量子点l仍然具有量子点典型的吸收峰,修饰后的量子点吸收峰相对于原来的量子点发生不同程度的红移,说明多胺衍生物已经成功修饰到了量子点上;由于cHCPT的加入,载药后的产物m的紫外光谱吸收光谱在375-430nm处出现了一个新的吸收带,表明cHCPT已经成功地修饰到量子点上。
利用荧光光谱对量子点(CdSe)及多胺衍生物修饰后的量子点l(CdSe@Polyamine)和载药后的产物m(CdSe@Polyamine-cHCPT)进行表征,结果见图3。图3可以看出:吸附了cHCPT后,荧光强度有所下降,发射光谱出现稍微的蓝移,同原来的量子点相比,载药后的产物m发射光谱带更宽,量子点之间荧光的差异是多胺衍生物以及cHCPT在其表面的复合引起的。
实施例2
制备R为苯丙氨酸残基时,多胺衍生物修饰的量子点纳米药物载体的合成步骤:
1)制备化合物b:参照实施例1;
2)制备化合物c:参照实施例1;
3)制备化合物d:参照实施例1;
4)制备化合物e:参照实施例1;
5)制备化合物f:参照实施例1;
6)制备化合物g:参照实施例1;
7)制备化合物h:参照实施例1;
8)制备化合物j:将苯丙氨酸i溶于50mL的甲醇溶剂中,加入(BOC)2O 5mmol,室温搅拌过夜,TLC监测。减压蒸除溶剂,残余物用40mL氯仿提取,3×40mL水洗涤,收集有机层,有机层用无水硫酸钠干燥,减压蒸除氯仿,硅胶柱(石油醚和乙酸乙酯体积比1:1洗脱)分离提纯得淡黄色化合物j;
9)制备化合物k:取1.33g(5mmol)化合物j溶于15mL的无水乙腈中,搅拌溶解,向其中加入0.96g(5mmol)1,2-二氯乙烷(EDC)和0.58g(5mmol)N-羟基丁二酰亚胺(NHS),继续搅拌2h,向其中加入5mmol化合物h,室温搅拌反应过夜,蒸干溶剂,向其中加入10mL CH2Cl2溶解油状物,并用10%Na2CO3水溶液洗涤、收集、干燥并蒸干有机层,得混浊的油状化合物,然后再向其中加入5mL蒸馏水,并用CH2Cl2洗涤,收集并真空蒸干水层,得白色的固体化合物k;
10)制备化合物l:参照实施例1;
11)制备化合物m:参照实施例1。
实施例3
制备R为色氨酸残基时,多胺衍生物修饰的量子点纳米药物载体的合成步骤:
1)制备化合物b:参照实施例1;
2)制备化合物c:参照实施例1;
3)制备化合物d:参照实施例1;
4)制备化合物e:参照实施例1;
5)制备化合物f:参照实施例1;
6)制备化合物g:参照实施例1;
7)制备化合物h:参照实施例1;
8)制备化合物j:将色氨酸i溶于50mL的甲醇溶剂中,加入(BOC)2O 5mmol,室温搅拌过夜,TLC监测。减压蒸除溶剂,残余物用40mL氯仿提取,3×40mL水洗涤,收集有机层,有机层用无水硫酸钠干燥,减压蒸除氯仿,硅胶柱(石油醚和乙酸乙酯体积比1:1洗脱)分离提纯得淡黄色化合物j;
9)制备化合物k:取1.52g(5mmol)化合物j溶于15mL的无水乙腈中,搅拌溶解,向其中加入0.96g(5mmol)1,2-二氯乙烷(EDC)和0.58g(5mmol)N-羟基丁二酰亚胺(NHS),继续搅拌2h,向其中加入5mmol化合物h,室温搅拌反应过夜,蒸干溶剂,向其中加入10mL CH2Cl2溶解油状物,并用10%Na2CO3水溶液洗涤、收集、干燥并蒸干有机层,得混浊的油状化合物,然后再向其中加入5mL蒸馏水,并用CH2Cl2洗涤,收集并真空蒸干水层,得白色的固体化合物k;
10)制备化合物l:参照实施例1;
11)制备化合物m:参照实施例1。
活性实验
细胞培养:HepG2(肝癌细胞)、HeLa(宫颈癌细胞)和QSG-7701(人肝癌细胞),细胞用含10%(v/v)胎牛血清(FBS)的1640培养基于培养瓶中培养,其中含有1%(v/v)的双抗(每毫升含100单位青霉素和100g链霉素),培养瓶置于37℃,含5%CO2且湿度为90%的培养箱中孵育。
细胞毒性测试:实施例1至3制备得到的多胺衍生物修饰的量子点l及载药后的产品m在HepG2,HeLa和7701细胞中的细胞毒性采用MTT法测定,具体如下:
将消化好的细胞以每孔5×104/mL的浓度接种到96孔板中,培养24h,吸去培养基,再分别加入用培养基稀释的不同浓度的实施例1至3制备得到的量子点l及载药后的产品m样品,继续培养48h。然后向每孔中加入20μL MTT(2.5mg/mL),继续在培养箱中培养4h,除去上清液,向每孔中加入100μL DMSO,振荡10min左右,然后用M200酶标仪测定OD值,波长设置为570nm和690nm双波长。没有加入样品的孔的细胞存活率作为对照,设为100%,计算细胞存活率,同时作图并求得半数杀伤浓度(IC50),评价样品的细胞毒性。结果见表1。
表1实施例1至3制备所得产物的细胞毒性
表1测试了实施例1、2和3制备得到的多胺衍生物修饰的量子点纳米药物载体l及载药后的产品m对HeLa、HepG2和QSG-7701细胞的体外生长抑制活性。IC5值为能使正常分裂生长的细胞数抑制到50%水平时的样品浓度值(μg/mL),IC50值越大表明样品的细胞毒性越弱。实验结果表明:本发明多胺衍生物修饰的量子点纳米药物载体l对细胞的毒性比较小,而载药后的产品m可以更有效地抑制多种癌细胞的生长,而且对正常细胞的损伤较小。
综上说明:本发明多胺衍生物修饰的量子点纳米药物载体l可以作为纳米药物载体使用,应用于药物化学领域,其可为更好地设计纳米药物载体奠定基础。
Claims (10)
2.如权利要求1所述多胺衍生物修饰的量子点,其特征在于,所述氨基酸为苯丙氨酸、色氨酸或半胱氨酸。
3.权利要求1或2所述多胺衍生物修饰的量子点的制备方法,其特征在于,合成路线如下所示:
具体包括如下步骤:
1)将邻苯二甲酰亚胺a溶于无水乙醇中,加入含氢氧化钾的无水乙醇溶液,析出的固体经干燥得邻苯二甲酰亚胺钾盐;然后和1,3二溴丙烷在有机溶剂丙酮中回流反应8-20h,冷却,经过滤、减压蒸馏和重结晶得到化合物b;
2)将Boc保护的丙二胺溶于乙腈中,加入碱性碳酸物和化合物b于30-60℃反应8-20h,经后处理得到化合物c;
3)将化合物c溶于甲醇中,加入二碳酸二叔丁酯后于室温反应8-20h,经后处理得到化合物d;
4)将化合物d溶于乙醇中,加入水合肼后于室温反应8-20h,反应结束经后处理得到化合物e;
5)将化合物e溶于乙腈中,加入碱性碳酸物和化合物b于30-60℃反应8-20h,经后处理得到化合物f;
6)将化合物f溶于甲醇中,加入二碳酸二叔丁酯后于室温反应8-20h,经后处理得到化合物g;
7)将化合物g溶于乙醇中,加入水合肼后于室温反应8-20h,反应结束经后处理得到化合物h;
8)以氨基酸i为原料,加入二碳酸二叔丁酯后于室温反应8-20h,经后处理得到氨基保护的氨基酸化合物j;
9)将化合物j溶于无水乙腈中,在1,2-二氯乙烷和N-羟基丁二酰亚胺作用下与化合物h于室温反应8-20h,经分离纯化得到多胺衍生物k;
10)将多胺衍生物k加入到CdSe量子点的氯仿溶液中,同时加入三乙胺,室温超声至量子点完全由有机层转入到上层水相中,加入适量乙酸乙酯震荡使产生沉淀,经离心、洗涤得到的沉淀物即为多胺衍生物修饰的量子点l。
4.如权利要求3所述多胺衍生物修饰的量子点的制备方法,其特征在于,步骤1)中所述邻苯二甲酰亚胺和氢氧化钾的摩尔比为1:2-4;步骤2)中所述碱性碳酸物为K2CO3或Na2CO3,碱性碳酸物的用量以调节溶液pH为8-10为准;化合物b和Boc保护的丙二胺的摩尔比为1:1-2。
5.如权利要求3所述多胺衍生物修饰的量子点的制备方法,其特征在于,步骤3)中所述化合物c与二碳酸二叔丁酯的摩尔比为1:2-4;步骤4)中所述化合物d和水合肼的摩尔比为1:10-20。
6.如权利要求3所述多胺衍生物修饰的量子点的制备方法,其特征在于,步骤5)中所述碱性碳酸物为K2CO3或Na2CO3,碱性碳酸物的用量以调节溶液pH为8-10为准;化合物b和化合物e的摩尔比为1:1-2。
7.如权利要求3所述的多胺衍生物修饰的量子点的制备方法,其特征在于,步骤6)中所述化合物f和二碳酸二叔丁酯的摩尔比为1:1-3;步骤7)中所述化合物g和水合肼的摩尔比为1:10-20。
8.如权利要求3所述多胺衍生物修饰的量子点的制备方法,其特征在于,步骤9)中所述化合物h与化合物j的摩尔比为1:1-2;步骤10)中量子点与多胺衍生物k的摩尔比为1:6-7。
9.权利要求1或2所述多胺衍生物修饰的量子点作为纳米药物载体在载药方面的应用。
10.权利要求1或2所述多胺衍生物修饰的量子点作为纳米药物载体在细胞生物活性方面的应用。
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