In vivo tumor targeting and image-guided drug delivery with antibody-conjugated, radiolabeled mesoporous silica nanoparticles.
In vivo tumor targeting and image-guided drug delivery with antibody-conjugated, radiolabeled mesoporous silica nanoparticles.
复制标题
DOI：
10.1021/nn403617j
复制
发表时间：
2013-10-22
期刊：
影响因子：
17.1
通讯作者：
Cai W
中科院分区：
文献类型：
--
作者：
Chen F;Hong H;Zhang Y;Valdovinos HF;Shi S;Kwon GS;Theuer CP;Barnhart TE;Cai W
自从首次使用生物相容性介孔二氧化硅（mSiO2）纳米颗粒作为药物递送载体以来，体内肿瘤靶向成像和增强抗癌药物递送一直是一个主要挑战。在这项工作中，我们描述了功能化二氧化硅纳米颗粒的发展，用于主动靶向正电子发射断层扫描（PET）成像和4T1小鼠乳腺肿瘤的药物递送。我们的结构设计包括合成、巯基表面功能化、聚乙二醇化、TRC105抗体（特异性CD105/内啡肽）偶联和64cu标记均匀80 nm大小的二氧化硅纳米颗粒。系统的体内肿瘤靶向研究清楚地表明，64Cu-NOTA-mSiO2-PEG-TRC105可以通过增强通透性和滞留效应以及trc105介导的与肿瘤血管CD105的结合，在4T1肿瘤部位显著积累。作为概念验证，我们还证明了在静脉注射含有DOX的NOTA-mSiO2-PEG-TRC105后，4T1肿瘤小鼠成功增强了多柔比辛（DOX）的肿瘤靶向递送，这在未来的图像引导药物递送和靶向癌症治疗中具有很大的潜力。
Since the first use of biocompatible mesoporous silica (mSiO2) nanoparticles as drug delivery vehicles, in vivo tumor targeted imaging and enhanced anti-cancer drug delivery has remained a major challenge. In this work, we describe the development of functionalized mSiO2 nanoparticles for actively targeted positron emission tomography (PET) imaging and drug delivery in 4T1 murine breast tumor-bearing mice. Our structural design involves the synthesis, surface functionalization with thiol groups, PEGylation, TRC105 antibody (specific for CD105/endoglin) conjugation, and 64Cu-labeling of uniform 80 nm sized mSiO2 nanoparticles. Systematic in vivo tumor targeting studies clearly demonstrated that 64Cu-NOTA-mSiO2-PEG-TRC105 could accumulate prominently at the 4T1 tumor site via both the enhanced permeability and retention effect and TRC105-mediated binding to tumor vasculature CD105. As a proof-of-concept, we also demonstrated successful enhanced tumor targeted delivery of doxorubicin (DOX) in 4T1 tumor-bearing mice after intravenous injection of DOX-loaded NOTA-mSiO2-PEG-TRC105, which holds great potential for future image-guided drug delivery and targeted cancer therapy.