CN114848852A - 一种自组装石墨烯量子点纳米粒子及其制备方法及其应用 - Google Patents

一种自组装石墨烯量子点纳米粒子及其制备方法及其应用 Download PDF

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CN114848852A
CN114848852A CN202110076014.1A CN202110076014A CN114848852A CN 114848852 A CN114848852 A CN 114848852A CN 202110076014 A CN202110076014 A CN 202110076014A CN 114848852 A CN114848852 A CN 114848852A
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graphene quantum
self
quantum dot
polyethylene glycol
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CN114848852B (zh
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周欣
杨玉琪
王宝龙
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Institute of Precision Measurement Science and Technology Innovation of CAS
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Abstract

本发明公开了一种自组装石墨烯量子点纳米粒子及其制备方法及其应用。通过聚乙二醇将客体自组装金刚烷连接于石墨烯量子点上，在水溶液中与主体自组装模块多臂聚乙二醇环糊精发生主客体作用，自组装形成纳米粒。此纳米粒可作为多种药物小分子的载体，实现光学成像、质子磁共振成像等多种模态成像，也可用于癌症治疗研究。此纳米粒可明显延长小分子药物体循环时间，降低活体毒性；可长时间富集在肿瘤部位和肺部，为活体肺部肿瘤的多模态成像和治疗研究提供可能。本纳米系统为一系列合成简单、性质优良的多模态活体造影剂，将有望应用于生物医药领域。

Description

一种自组装石墨烯量子点纳米粒子及其制备方法及其应用
技术领域
本发明属于磁共振成像技术领域，具体涉及一种自组装石墨烯量子点纳米粒子及其制备方法及其应用。
背景技术
基于药物的肿瘤诊断和治疗通过多种机制起到诊疗的效果，具有诊疗系统性和患者顺应性高等优点，是目前临床最重要的肿瘤诊疗手段方法之一。但是传统的小分子药物也表现出了诸多弊端：(1)在体内容易在较短时间内被降解清除，降低药物效果；(2)在体内的非特异性分布会引起全身毒性；(3)重复多次给药引发耐药性。这些问题严重阻碍了小分子药物诊疗的进一步发展。近年来兴起的纳米药物载体可以有效改善上述缺点。纳米药物载体可以经过血液循环进入毛细血管，还可透过内皮细胞间隙被细胞以胞饮方式吸收，实现靶向用药从而提高了药物的生物利用度；纳米载体粒径较小而比表面积较高，可以装载疏水性药物，减少常规用药中助溶剂的副作用；纳米载体表面可修饰主动靶向基团实现靶向给药，从而减少了用药剂量降低副作用，甚至普通纳米粒都可以通过被动靶向ERP效应在肿瘤部位高效富集；纳米载体可大大延长药物的半衰期，提高有效血药浓度时间，降低用药频率减小副作用；纳米载体可响应肿瘤微环境定点释放药物从而减小全身毒性。
石墨烯量子点(Graphene QuantumDots,GQDs)是一种具有完美化学物理和生物性质的二维碳基纳米材料，已在纳米药物等领域有广泛应用。其独特的大共轭电子结构使其具有强烈且可变的荧光，使其应用于荧光成像和生物探针领域。并且这种结构可以与芳香性药物产生共轭效应从而将药物负载在其上面；所以石墨烯量子点在药物传递方面也有大量应用。石墨烯量子点也可以吸收激光照射产生光热和光动力效果，这使得它在肿瘤的光热和光动力治疗方面也有应用。但石墨烯量子点一般粒径小于10nm，使得其在活体内代谢较快，药物负载量较小，难以发挥纳米材料应有的优势。
石墨烯量子点的大共轭电子结构可以负载大部分共轭芳香性药物，广泛应用于生物成像，生物传感和活体治疗方面。例如常见的光敏剂四羧苯基卟啉能够接受长红外波长激光的照射产生荧光和光动力效应，是一类很好的光致发光试剂和光动力治疗药物；其具有的共轭结构也能和石墨烯量子点共轭而被负载在石墨烯量子点表面(ACSAppl.Mater.Interfaces,2017,9,159-166)。将锰和四羧苯基卟啉鳌合形成的锰四羧苯基卟啉则是一种很好的具有共轭效应的T1弛豫磁共振造影剂(Chem.Res.Chin.Univ.,2014,30(4),549-555)。
发明内容
本发明的目的在于克服现有技术的不足，提供一种自组装石墨烯量子点纳米粒子的制备方法及其在药物运载中的应用；本发明提供的自组装石墨烯量子点纳米粒结合了荧光成像活体T1磁共振成像实现了对肺癌肿瘤的精准诊断；并且使用主客体自组装技术将二维石墨烯量子点制备成纳米粒，延长了体循环时间，提高了载药量，且延长了在肿瘤部位的富集时间。该显影剂有超高灵敏度和良好生物相容性；该纳米粒制备方法简单，原料便宜易得；且能负载具有共轭结构的药物；适合用于体内多模态成像和肿瘤治疗。
本发明制备了一种高生物相容性的纳米药物载体，并通过π-π作用将带有共轭体系的亲疏水性小分子药物载入其中；在有效延长体循环时间的同时降低了其它副作用；并可用于磁共振成像、计算机断层成像和荧光成像等多模态成像模式，还可用于光动力治疗和光热治疗等多种新型治疗方式。
本发明将石墨烯量子点通过主客体自组装形成粒径大于100nm的纳米粒，明显延长体循环时间，提高载药量，且能将荧光成像、磁共振成像、光热效应、光动力效应有机结合在一起。
实现本发明上述目的所采用的技术方案为：
一种自组装石墨烯量子点纳米粒子，所述的自组装石墨烯量子点纳米粒子为石墨烯量子点-聚乙二醇-金刚烷/环糊精-多臂聚乙二醇载体，多臂聚乙二醇与环糊精共价连接，多臂聚乙二醇与环糊精的摩尔比为5μmol：400μmol，所述环糊精为6-苯磺酸-β-环糊精；多臂聚乙二醇的平均分子量为10KDa，聚乙二醇为直链结构，平均分子量为2KDa，金刚烷、石墨烯量子点分别与聚乙二醇的两端共价连接；聚乙二醇与金刚烷的反应摩尔比为0.1：1，石墨烯量子点与聚乙二醇-金刚烷的反应质量比为15mg：50mg，石墨烯量子点-聚乙二醇-金刚烷与环糊精-多臂聚乙二醇按投料比为1：1自组装。
一种自组装石墨烯量子点纳米粒，由所述的自组装石墨烯量子点纳米粒子的石墨烯量子点通过π-π共轭作用连接含共轭结构的小分子药物形成，含共轭结构的小分子药物与石墨烯量子点-聚乙二醇-金刚烷的投料比为：0.01mmol含共轭结构的小分子药物：5mg石墨烯量子点-聚乙二醇-金刚烷。
进一步地，所述多臂聚乙二醇为八臂聚乙二醇。
进一步地，所述石墨烯量子点粒径小于20nm。
进一步地，所述小分子药物包括含苯环基团的小分子。
进一步地，所述小分子药物包括四羧苯基卟啉、锰四羧苯基卟啉。
一种自组装石墨烯量子点纳米粒的制备方法，包括如下步骤：
(4)石墨烯量子点-聚乙二醇-金刚烷的制备：将1-金刚烷酰氯和Boc-PEG-NH2溶解于无水二氯甲烷，加入催化量三乙胺室温搅拌过夜，反应结束后旋蒸除去二氯甲烷，残渣用水溶解后离心除去沉淀，上清液加入体积1/10的三氟乙酸搅拌过夜，将所得溶液旋蒸除去三氟乙酸后加入石墨烯量子点溶液中，再加入缩合剂EDC、NHS和催化量三乙胺，室温搅拌48小时，即得石墨烯量子点-聚乙二醇-金刚烷，记为GQD-PEG-Ad；
(5)多臂聚乙二醇-环糊精的制备：将多臂聚乙二醇和6-苯磺酸-β-环糊精溶解于DMSO中，70℃反应72小时；反应完毕后超纯水透析72小时除去DMSO即得多臂聚乙二醇-环糊精，记为mPEG-CD；
(6)载药自组装石墨烯量子点纳米粒的制备：向GQDs-PEG-Ad水溶液中加入相同体积等浓度的mPEG-CD水溶液搅拌12小时，使金刚烷和环糊精在水相中完成亲疏水自组装，即得自组装石墨烯量子点纳米粒，记为GQD NP。
其中Boc-PEG-NH2分子量为2KDa，mPEG-NH2分子量为10KDa；石墨烯量子点为氧化羟基化碳纳米管所得。
进一步地，所述步骤(3)为：将含共轭结构的小分子药物溶于DMSO中，加入相同体积的GQD-PEG-Ad的水溶液，然后置于摇床上以300rpm的速度振荡24小时，然后加入mPEG-CD水溶液搅拌12小时，分离除去二甲基亚砜和残余的小分子药物，即得载药自组装石墨烯量子点纳米粒。
一种自组装石墨烯量子点纳米粒在药物运载中的应用，所述自组装石墨烯量子点纳米粒多模态成像显影剂能在体内循环72h以上，且在肿瘤部位富集。
一种自组装石墨烯量子点纳米粒在磁共振成像和光动力治疗的药物中的应用，其特征在于，所述小分子药物为锰四羧苯基卟啉时，所述自组装石墨烯量子点纳米粒能在肿瘤部位富集，并在7T核磁共振成像仪中进行T1成像；所述小分子药物为四羧苯基卟啉时，所述自组装石墨烯量子点纳米粒能作为光动力治疗的药物，在mM级浓度具有明显紫外吸收。
与现有技术相比，本发明的有益效果和优点在于：
1、本发明所制备的纳米粒子能通过电子共轭效应负载药物。
2、本发明所制备的纳米磁共振造影剂纵向弛豫效率r1为12.6mmol-1s-1，纵向弛豫效果明显好于商用磁共振造影剂马根维显(Gd-DTPA，3.8mmol-1s-1)或多它灵(Gd-DOTA，3.5mmol-1s-1)。
3、纳米荧光造影剂能在体内循环72h以上，且在肿瘤部位富集，在激光照射下对肿瘤治疗效果明显。相比于石墨烯量子点，本发明制备的自组装石墨烯量子点纳米粒能明显延长体循环时间。
4、本发明纳米粒所使用得纳米粒得主体是石墨烯量子点和聚乙二醇，材料便宜易得，生物相容性优良且纳米粒制备简单。且能负载具有共轭结构的小分子药物。
5、本发明所制备的纳米粒能负载小分子药物既能作为光学成像和1H MRI成像显影剂，是一种性能良好的多模态造影剂。也可用于疾病的多种模式治疗。
附图说明
图1为本发明实施例1中中间产物的结构表征图；
图2为本发明实施例1中GQDs-PEG-Ad的结构表征图；
图3为本发明实施例1中mPEG-CD的结构表征图；
图4为本发明实施例1制备的GQD NP的动态光散射图；
图5为本发明实施例1制备的GQD NP的透射电镜图；
图6为本发明实施例1制备的GQD NP的光热转换图及温度量化图；
图7为本发明实施例1制备的GQD NP的升降温循环图；
图8为本发明实施例1制备的GQD NP的降温时间与-Inθ线性拟合图；
图9为本发明实施例2和实施例3制备的载药纳米粒的紫外吸收图；
图10为本发明实施例2制备的Mn-TCPP-GQD NP的活体磁共振成像图；
图11为本发明实施例3制备的不同浓度的TCPP-GQD NP紫外吸收图；
图12为本发明实施例3制备的不同浓度的TCPP-GQD NP线性拟合图；
图13为本发明实施例3制备的TCPP-GQD NP的细胞光疗图；
图14为本发明实施例4制备的TCPP-GQD NP的活体荧光成像图。
具体实施方式
下面以具体实施例子，进一步阐述本发明。下述实施例仅用于说明本发明而不用于限制本发明的范围。
实施例1
一种自组装石墨烯量子点纳米粒及其制备方法和应用
具体的实验步骤如下：
(1)石墨烯量子点-聚乙二醇-金刚烷的制备：将1-金刚烷酰氯(50mg,0.25mmol)和二碳酸二叔丁酯单保护的氨基聚乙二醇(Boc-PEG-NH2)(50mg,0.025mmol,Mw 2000Da)溶解于无水二氯甲烷(DCM)，加入催化量(10μL)三乙胺(TEA)室温搅拌过夜，得到中间体I。
反应结束后旋蒸除去二氯甲烷，残渣用水溶解后离心除去过量未反应的金刚烷甲酸沉淀，取上清液加入上清液体积1/10的三氟乙酸(TFA)搅拌过夜脱去Boc，得到中间体II，若继续除杂后得50mg中间体II。
将所得溶液旋蒸除去三氟乙酸后加入石墨烯量子点(GQDs)水溶液(15mg,10mL)中，再加入缩合剂：1-乙基-(3-二甲基氨基丙基)碳二亚胺(EDC)(248mg,1.6mmol)、N-羟基琥珀酰亚胺(NHS)(184mg,1.6mmol)和催化量三乙胺(10μL)，室温搅拌48小时，利用EDC和NHS在常温下活化GQDs表面的羧基端，使其与中间体II的氨基端共价连接，即得石墨烯量子点-聚乙二醇-金刚烷，记为GQDs-PEG-Ad。
本发明的步骤(1)首先使用带保护基的聚乙二醇与金刚烷酰氯反应，可以使金刚烷定点高效的接枝到聚乙二醇一端，再将聚乙二醇另一端脱保护后连接到GQDs表面，使最
Figure BDA0002907650230000051
终产物具有确定结构，减少了副产物的生成。
反应路线如上，产物结构表征如图1和图2：
(2)八臂聚乙二醇-环糊精的制备：将八臂聚乙二醇(50mg,5μmol，Mw 10KDa)和6-苯磺酸-β-环糊精(516mg,0.4mmol)溶解于二甲基亚砜(DMSO)中，70℃反应72小时；反应完毕后超纯水透析72小时除去二甲基亚砜(DMSO)即得八臂聚乙二醇-环糊
Figure BDA0002907650230000052
精，记为mPEG-CD。反应路线如下，产物结构表征如图4：
(3)载药自组装石墨烯量子点纳米粒的制备：向GQDs-PEG-Ad水溶液(1mg/mL)中加入相同体积的mPEG-CD水溶液(1mg/mL)搅拌12小时。使金刚烷和环糊精在水相中完成亲疏水自组装。即得自组装石墨烯量子点纳米粒，记为GQD NP。
将本实施例1制备的GQD NP进行动态光散射检测，所得的动态光散射图如图4所示，平均水合粒径148±6.5nm。
将本实施例1制备的GQD NP进行透射电镜扫描，所得透射电镜图如图5所示，本实施例制备的纳米粒为类球形。
将本实施例1制备的GQD NP使用650nm近红外激光照射(100mW)，如图6a和图6b所示可见明显的光热转换。但与对照组GQDs相比无明显差别，说明GQD NP的光热效果主要来自于GQDs。图7为GQD NP的升降温循环曲线图，表明GQD NP光热转换效果稳定。图8为降温时间与-ln(ΔT)之间的线性拟合图。
实施例2
自组装石墨烯量子点纳米粒在磁共振成像中的应用举例
载锰四羧苯基卟啉自组装石墨烯量子点纳米粒的制备：将小分子药物锰四羧苯基卟啉(0.01mmol)溶于二甲基亚砜(DMSO)中，加入相同体积的石墨烯量子点-聚乙二醇-金刚烷(GQDs-PEG-Ad)的水溶液(1mg/mL)，然后置于摇床上以300rpm的速度振荡24小时，之后加入八臂聚乙二醇-环糊精(mPEG-CD)水溶液(1mg/mL)搅拌12小时。完毕后用去离子水透析48小时除去二甲基亚砜(DMSO)，离心除去游离的卟啉，上清液即为载药自组装石墨烯量子点纳米粒(Mn-TCPP-GQD NP)。
将本实施例2制备的GQD NP装载四羧苯基卟啉(TCPP-GQD NP)和锰四羧苯基卟啉(Mn-TCPP-GQD NP)后进行紫外-可见光分光光度计测试，如图9所示纳米粒具有卟啉的紫外吸收特征峰说明纳米粒成功装载了两种药物。卟啉的最大紫外吸收峰由420nm红移到450nm，主要是因为纳米粒装载卟啉后，GQDs与卟啉、卟啉与卟啉和三者之间的大π-π共轭效应导致。
Mn-TCPP-GQD NP溶液(50mg/mL，200μL)尾静脉注射入荷瘤裸鼠模型。并在7T核磁共振成像仪中进行T1成像，TR/TE＝500/11ms,FOV＝40*40mm2,MTX＝128*128,Slice＝3。如图10所示，可看出本纳米粒可明显增强肿瘤部位的亮度，说明纳米粒在肿瘤部位富集并成功减小了水的纵向弛豫时间。
实施例3
自组装石墨烯量子点纳米粒在光动力治疗中的应用举例
载四羧苯基卟啉自组装石墨烯量子点纳米粒的制备：将小分子药物四羧苯基卟啉(0.01mmol)溶于二甲基亚砜(DMSO)中，加入相同体积的石墨烯量子点-聚乙二醇-金刚烷(GQDs-PEG-Ad)的水溶液(1mg/mL)，然后置于摇床上以300rpm的速度振荡24小时，然后加入八臂聚乙二醇-环糊精(mPEG-CD)水溶液(1mg/mL)搅拌12小时。完毕后用去离子水透析48小时除去二甲基亚砜(DMSO)，离心除去游离的卟啉，上清液即为载药自组装石墨烯量子点纳米粒(TCPP-GQD NP)。将载四羧苯基卟啉的自组装石墨烯量子点纳米粒配置成不同浓度并测试其西外吸收曲线，如图11和图12所示，图11中的各吸收曲线按对应载药自组装石墨烯量子点纳米粒的浓度依次递减自上向下排列，纳米粒在mM级浓度既有明显紫外吸收且与浓度成线性关系，说明疏水性小分子卟啉被成功负载于纳米粒中，无明显泄露现象。
(2)将本实施例制备的TCPP-GQD NP与腺癌人类肺泡基底上皮细胞(A549细胞)共同孵育，再用波长640nm的激光照射对A549细胞进行细胞光动力治疗；用活细胞/死细胞双染试剂盒(calcein-AM/PI试剂盒)，标记细胞后通过荧光共聚焦显微镜观察。如图13所示在激光照射区域细胞全部为红色荧光(图13中的深色点)，而在未照射区域细胞为绿色荧光(图13中的浅色点)，说明光疗区域癌细胞全部凋亡，纳米粒对细胞光动力治疗效果明显。
其中，Calcein-AM是一种对活细胞进行荧光标记的细胞染色试剂，发绿色荧光(Ex＝490nm,Em＝515nm)。因其在传统的Calcein(钙黄绿素)基础上引入乙酰甲氧基甲酯(AM)基团，增加了疏水性，使其能够轻易穿透活细胞膜，一旦进入细胞后，Calcein-AM(本身不发荧光)被细胞内的酯酶剪切形成膜非渗透性的极性分子Calcein，从而被滞留在细胞内并发出强绿色荧光。由于死细胞缺乏酯酶，Calcein-AM仅用于对活细胞的细胞生存能力测试和短期标记。因此，Calcein-AM常常与死细胞荧光探针如碘化丙啶(PI)等联合使用，同时进行活细胞和死细胞的荧光双重染色。碘化丙啶(Propidium iodide，PI)不能穿过活细胞的细胞膜，仅能穿过死细胞膜的无序区域而到达细胞核，并嵌入细胞的DNA双螺旋从而产生红色荧光(Ex＝535nm,Em＝617nm)，因此PI仅对死细胞染色。由于Calcein和PI-DNA都可被490nm激发，因此可用荧光显微镜同时观察活细胞和死细胞。而用545nm激发，仅可观察到死细胞。
实施例4
自组装石墨烯量子点纳米粒在活体荧光成像中的应用举例
(1)将实施例3中制备的TCPP-GQD NP溶液(5mg/mL，200μL)尾静脉注射入荷瘤裸鼠模型。荷瘤裸鼠模型是研究中最常使用的是移植瘤模型，主要包括原位移植瘤和皮下移植瘤。简言之，就是将相关的肿瘤细胞通过原位注射或者通过皮下注射入小鼠(一般为小鼠)体内，使其致瘤。并利用活体荧光成像仪进行荧光成像，所使用激发光波长为640nm，发射光波长为720nm，曝光时间为1s。如图14所示，TCPP-GQD NP在体内循环时间在60h以上，在28h时在肿瘤部位富集最多。
上述实施例只是为了说明本发明的技术构思及特点，其目的是在于让本领域内的普通技术人员能够了解本发明的内容并据以实施，并不能以此限制本发明的保护范围。凡是根据本发明内容的实质所作出的等效的变化或修饰，都应涵盖在本发明的保护范围内。

Claims (10)

1.一种自组装石墨烯量子点纳米粒子，其特征在于，所述的自组装石墨烯量子点纳米粒子为石墨烯量子点-聚乙二醇-金刚烷/环糊精-多臂聚乙二醇载体，多臂聚乙二醇与环糊精共价连接，多臂聚乙二醇与环糊精的摩尔比为5μmol：400μmol，所述环糊精为6-苯磺酸-β-环糊精；多臂聚乙二醇的平均分子量为10KDa，聚乙二醇为直链结构，平均分子量为2KDa，金刚烷、石墨烯量子点分别与聚乙二醇的两端共价连接；聚乙二醇与金刚烷的反应摩尔比为0.1：1，石墨烯量子点与聚乙二醇-金刚烷的反应质量比为15mg：50mg，石墨烯量子点-聚乙二醇-金刚烷与环糊精-多臂聚乙二醇按投料比为1：1自组装。
2.根据利要求1所述的自组装石墨烯量子点纳米粒，其特征在于，由所述的自组装石墨烯量子点纳米粒子的石墨烯量子点通过π-π共轭作用连接含共轭结构的小分子药物形成，含共轭结构的小分子药物与石墨烯量子点-聚乙二醇-金刚烷的投料比为：0.01mmol含共轭结构的小分子药物：5mg石墨烯量子点-聚乙二醇-金刚烷。
3.根据利要求2所述的自组装石墨烯量子点纳米粒，其特征在于，所述多臂聚乙二醇为八臂聚乙二醇。
4.根据利要求2所述的自组装石墨烯量子点纳米粒，其特征在于，所述石墨烯量子点粒径小于20nm。
5.根据利要求2所述的自组装石墨烯量子点纳米粒，其特征在于，所述小分子药物包括含苯环基团的小分子。
6.根据利要求5所述的自组装石墨烯量子点纳米粒，其特征在于，所述小分子药物包括四羧苯基卟啉、锰四羧苯基卟啉。
7.如权利要求2～6任一一项所述的自组装石墨烯量子点纳米粒的制备方法，其特征在于，包括如下步骤：
(1)石墨烯量子点-聚乙二醇-金刚烷的制备：将1-金刚烷酰氯和Boc-PEG-NH2溶解于无水二氯甲烷，加入催化量三乙胺室温搅拌过夜，反应结束后旋蒸除去二氯甲烷，残渣用水溶解后离心除去沉淀，上清液加入体积1/10的三氟乙酸搅拌过夜，将所得溶液旋蒸除去三氟乙酸后加入石墨烯量子点溶液中，再加入缩合剂EDC、NHS和催化量三乙胺，室温搅拌48小时，即得石墨烯量子点-聚乙二醇-金刚烷，记为GQD-PEG-Ad；
(2)多臂聚乙二醇-环糊精的制备：将多臂聚乙二醇和6-苯磺酸-β-环糊精溶解于DMSO中，70℃反应72小时；反应完毕后超纯水透析72小时除去DMSO即得多臂聚乙二醇-环糊精，记为mPEG-CD；
(3)载药自组装石墨烯量子点纳米粒的制备：向GQDs-PEG-Ad水溶液中加入相同体积等浓度的mPEG-CD水溶液搅拌12小时，使金刚烷和环糊精在水相中完成亲疏水自组装，即得自组装石墨烯量子点纳米粒，记为GQD NP。
其中Boc-PEG-NH2分子量为2KDa，mPEG-NH2分子量为10KDa；石墨烯量子点为氧化羟基化碳纳米管所得。
8.根据权利要求7所述的自组装石墨烯量子点纳米粒的制备方法，其特征在于，所述步骤(3)为：将含共轭结构的小分子药物溶于DMSO中，加入相同体积的GQD-PEG-Ad的水溶液，然后置于摇床上以300rpm的速度振荡24小时，然后加入mPEG-CD水溶液搅拌12小时，分离除去二甲基亚砜和残余的小分子药物，即得载药自组装石墨烯量子点纳米粒。
9.如权利要求2～6任一一项所述的自组装石墨烯量子点纳米粒在荧光成像药物中的应用。
10.如权利要求6所述的自组装石墨烯量子点纳米粒在磁共振成像和光动力治疗的药物中的应用，其特征在于，所述小分子药物为锰四羧苯基卟啉时，所述自组装石墨烯量子点纳米粒能在肿瘤部位富集，并在7T核磁共振成像仪中进行T1成像；所述小分子药物为四羧苯基卟啉时，所述自组装石墨烯量子点纳米粒能作为光动力治疗的药物。
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