Theranostic unimolecular micelles based on brush-shaped amphiphilic block copolymers for tumor-targeted drug delivery and positron emission tomography imaging.
Theranostic unimolecular micelles based on brush-shaped amphiphilic block copolymers for tumor-targeted drug delivery and positron emission tomography imaging.
复制标题
DOI：
10.1021/am5002585
复制
发表时间：
2014-12-24
影响因子：
9.5
通讯作者：
Gong, Shaoqin
中科院分区：
文献类型：
--
作者：
Guo, Jintang;Hong, Hao;Chen, Guojun;Shi, Sixiang;Nayak, Tapas R.;Theuer, Charles P.;Barnhart, Todd E.;Cai, Weibo;Gong, Shaoqin
关键词：
将刷状两亲嵌段共聚物与抗CD 105的单克隆抗体（即，TRC 105）和用于64 Cu标记的大环螯合剂以产生多功能治疗诊断单分子胶束。该刷状两亲性嵌段共聚物的主链为聚甲基丙烯酸2-羟乙酯（PHEMA），侧链为聚乳酸-聚乙二醇（PLLA-PEG）。阿霉素（DOX）单分子胶束具有pH依赖性的药物释放曲线和均匀的粒径分布。由于CD 105介导的内吞作用，在CD 105阳性人脐静脉内皮细胞（HUVEC）中观察到TRC 105缀合胶束的细胞摄取显著高于非靶向胶束。相反，在MCF-7人乳腺癌细胞（CD 105阴性）中观察到靶向和非靶向胶束的相似且极低的细胞摄取。在4 T1小鼠乳腺肿瘤荷瘤小鼠中，通过连续正电子发射断层扫描（PET）成像研究了64 Cu标记的TRC 105缀合胶束和非靶向胶束的体内肿瘤蓄积之间的差异，并通过生物分布研究进行了验证。这些多功能单分子胶束提供pH响应性药物释放，非侵入性PET成像能力，以及被动和主动肿瘤靶向能力，从而使它们成为癌症治疗诊断学的理想纳米平台。
Brush-shaped amphiphilic block copolymers were conjugated with a monoclonal antibody against CD105 (i.e., TRC105) and a macrocyclic chelator for 64Cu-labeling to generate multifunctional theranostic unimolecular micelles. The backbone of the brush-shaped amphiphilic block copolymer was poly(2-hydroxyethyl methacrylate) (PHEMA) and the side chains were poly(l-lactide)-poly(ethylene glycol) (PLLA-PEG). The doxorubicin (DOX)-loaded unimolecular micelles showed a pH-dependent drug release profile and a uniform size distribution. A significantly higher cellular uptake of TRC105-conjugated micelles was observed in CD105-positive human umbilical vein endothelial cells (HUVEC) than nontargeted micelles due to CD105-mediated endocytosis. In contrast, similar and extremely low cellular uptake of both targeted and nontargeted micelles was observed in MCF-7 human breast cancer cells (CD105-negative). The difference between the in vivo tumor accumulation of 64Cu-labeled TRC105-conjugated micelles and that of nontargeted micelles was studied in 4T1 murine breast tumor-bearing mice, by serial positron emission tomography (PET) imaging and validated by biodistribution studies. These multifunctional unimolecular micelles offer pH-responsive drug release, noninvasive PET imaging capability, together with both passive and active tumor-targeting abilities, thus making them a desirable nanoplatform for cancer theranostics.
登录
查看更多内容
影响因子：
14
作者：
Guo, Jintang;Hong, Hao;Chen, Guojun;Shi, Sixiang;Zheng, Qifeng;Zhang, Yin;Theuer, Charles P.;Barnhart, Todd E.;Cai, Weibo;Gong, Shaoqin
通讯作者：
Gong, Shaoqin
影响因子：
4.9
作者：
Engle JW;Hong H;Zhang Y;Valdovinos HF;Myklejord DV;Barnhart TE;Theuer CP;Nickles RJ;Cai W
通讯作者：
Cai W
DOI：
10.1016/j.ijbiomac.2009.01.007
发表时间：
2009-05-01
影响因子：
8.2
作者：
Aryal, Santosh;Prabaharan, Mani;Gong, Shaoqin
通讯作者：
Gong, Shaoqin
影响因子：
17.1
作者：
Hong H;Yang K;Zhang Y;Engle JW;Feng L;Yang Y;Nayak TR;Goel S;Bean J;Theuer CP;Barnhart TE;Liu Z;Cai W
通讯作者：
Cai W
影响因子：
15
作者：
Geng, Y;Discher, DE
通讯作者：
Discher, DE