Image-guided and tumor-targeted drug delivery with radiolabeled unimolecular micelles.
Image-guided and tumor-targeted drug delivery with radiolabeled unimolecular micelles.
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DOI：
10.1016/j.biomaterials.2013.07.085
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发表时间：
2013-11
期刊：
影响因子：
14
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;Zheng, Qifeng;Zhang, Yin;Theuer, Charles P.;Barnhart, Todd E.;Cai, Weibo;Gong, Shaoqin
关键词：
合成并表征了树枝状两亲嵌段共聚物聚酰胺-胺-聚乳酸-b-聚乙二醇（PAMAM-PLA-b-PEG-TRC 105）与抗CD 105单克隆抗体（TRC 105）和1，4，7-三氮杂环壬烷-N，N '，N-三乙酸（NOTA，~（64）Cu的大环螯合剂）形成的单分子胶束。采用物理包封的方法将抗癌模型药物阿霉素（DOX）负载到由聚乳酸（PLA）和聚酰胺-胺（PAMAM）形成的单分子胶束的疏水核中。该单分子胶束具有均一的粒径分布和pH敏感的释药行为。与非靶向单分子胶束相比，TRC 105缀合的单分子胶束在人脐静脉内皮细胞（HUVEC）中显示出CD 105相关的细胞摄取，这通过CD 105阴性MCF-7细胞中的细胞摄取进一步验证。在4 T1小鼠乳腺肿瘤荷瘤小鼠中，64 Cu标记的靶向胶束表现出比64 Cu标记的非靶向胶束高得多的肿瘤蓄积水平，通过连续非侵入性正电子发射断层扫描（PET）成像测量并通过生物分布研究证实。这些由树枝状两亲嵌段共聚物形成的单分子胶束将被动和主动肿瘤靶向能力与pH控制药物释放和PET成像能力协同整合，为未来的癌症治疗诊断学提供了基础。
Unimolecular micelles formed by dendritic amphiphilic block copolymers poly(amidoamine)–poly(l-lactide)-b-poly(ethylene glycol) conjugated with anti-CD105 monoclonal antibody (TRC105) and 1,4,7-triazacyclononane-N, N’, N-triacetic acid (NOTA, a macrocyclic chelator for 64Cu) (abbreviated as PAMAM–PLA-b-PEG–TRC105) were synthesized and characterized. Doxorubicin (DOX), a model anti-cancer drug, was loaded into the hydrophobic core of the unimolecular micelles formed by PAMAM and PLA via physical encapsulation. The unimolecular micelles exhibited a uniform size distribution and pH-sensitive drug release behavior. TRC105-conjugated unimolecular micelles showed a CD105-associated cellular uptake in human umbilical vein endothelial cells (HUVEC) compared with non-targeted unimolecular micelles, which was further validated by cellular uptake in CD105-negative MCF-7 cells. In 4T1 murine breast tumor-bearing mice, 64Cu-labeled targeted micelles exhibited a much higher level of tumor accumulation than 64Cu-labeled non-targeted micelles, measured by serial non-invasive positron emission tomography (PET) imaging and confirmed by biodistribution studies. These unimolecular micelles formed by dendritic amphiphilic block copolymers that synergistically integrate passive and active tumor-targeting abilities with pH-controlled drug release and PET imaging capabilities provide the basis for future cancer theranostics.
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