A reexamination of active and passive tumor targeting by using rod-shaped gold nanocrystals and covalently conjugated peptide ligands.
A reexamination of active and passive tumor targeting by using rod-shaped gold nanocrystals and covalently conjugated peptide ligands.
复制标题
DOI：
10.1021/nn102055s
复制
发表时间：
2010-10-26
期刊：
影响因子：
17.1
通讯作者：
Nie S
中科院分区：
文献类型：
--
作者：
Huang X;Peng X;Wang Y;Wang Y;Shin DM;El-Sayed MA;Nie S
将纳米粒子靶向递送至实体肿瘤是癌症纳米医学中最重要和最具挑战性的问题之一，但详细的递送机制和设计原则仍然没有得到很好的理解。在这里，我们报告了一类细长的金纳米晶体（称为纳米棒），共价结合到肿瘤靶向肽的定量肿瘤摄取研究。使用金作为“示踪剂”的一个主要优点是，可以通过元素质谱法定量测定肿瘤和其他器官中积累的金（金不是动物中发现的天然元素）。因此，胶体金纳米棒用聚乙二醇（PEG）层稳定，并与三种不同的配体缀合：（i）识别表皮生长因子受体（EGFR）的单链可变片段（ScFv）肽;（ii）识别尿激酶纤溶酶原激活物受体（uPAR）的氨基末端片段（ATF）肽;和（iii）识别avb 3整联蛋白受体的环状RGD肽。定量药代动力学和生物分布数据显示，与非靶向对照相比，这些靶向配体仅略微改善异种移植肿瘤模型中的总金积累，但它们的使用可能会极大地改变细胞内和细胞外纳米颗粒分布。当金纳米棒通过静脉注射给药时，我们还发现肿瘤微环境的活性分子靶向（例如，成纤维细胞、巨噬细胞和血管）不显著影响肿瘤纳米颗粒摄取。这些结果表明，对于光热癌症治疗，金纳米棒给药的首选途径是肿瘤内注射，而不是静脉注射。
The targeted delivery of nanoparticles to solid tumors is one of the most important and challenging problems in cancer nanomedicine, but the detailed delivery mechanisms and design principles are still not well understood. Here we report quantitative tumor uptake studies for a class of elongated gold nanocrystals (called nanorods) that are covalently conjugated to tumor-targeting peptides. A major advantage in using gold as a “tracer” is that the accumulated gold in tumors and other organs can be quantitatively determined by elemental mass spectrometry (gold is not a natural element found in animals). Thus, colloidal gold nanorods are stabilized with a layer of polyethylene glycols (PEGs), and are conjugated to three different ligands: (i) a single-chain variable fragment (ScFv) peptide that recognizes the epidermal growth factor receptor (EGFR); (ii) an amino terminal fragment (ATF) peptide that recognizes the urokinase plasminogen activator receptor (uPAR); and (iii) a cyclic RGD peptide that recognizes the avb3 integrin receptor. Quantitative pharmacokinetic and biodistribution data show that these targeting ligands only marginally improve the total gold accumulation in xenograft tumor models in comparison with nontargeted controls, but their use could greatly alter the intracellular and extracellular nanoparticle distributions. When the gold nanorods are administered via intravenous injection, we also find that active molecular targeting of the tumor microenvironments (e.g., fibroblasts, macrophages, and vasculatures) does not significantly influence the tumor nanoparticle uptake. These results suggest that for photothermal cancer therapy, the preferred route of gold nanorod administration is intra-tumoral injection instead of intravenous injection.
登录
查看更多内容
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
10.8
作者：
Durr, Nicholas J.;Larson, Timothy;Ben-Yakar, Adela
通讯作者：
Ben-Yakar, Adela
影响因子：
10.8
作者：
Huang, Xiaohua;El-Sayed, Ivan H.;El-Sayed, Mostafa A.
通讯作者：
El-Sayed, Mostafa A.
影响因子：
2.8
作者：
Garanger, Elisabeth;Boturyn, Didier;Dumy, Pascal
通讯作者：
Dumy, Pascal
影响因子：
38.3
作者：
Geng, Yan;Dalhaimer, Paul;Discher, Dennis E.
通讯作者：
Discher, Dennis E.