A tissue factor-cascade-targeted strategy to tumor vasculature: a combination of EGFP-EGF1 conjugation nanoparticles with photodynamic therapy.
A tissue factor-cascade-targeted strategy to tumor vasculature: a combination of EGFP-EGF1 conjugation nanoparticles with photodynamic therapy.
复制标题
同时优化肿瘤微环境和纳米医学特性以改善肿瘤治疗
DOI：
10.18632/oncotarget.12922
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发表时间：
2017-05-09
期刊：
影响因子：
--
通讯作者：
Hu Y
中科院分区：
文献类型：
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作者：
Shi W;Yin Y;Wang Y;Zhang B;Tan P;Jiang T;Mei H;Deng J;Wang H;Guo T;Pang Z;Hu Y
肿瘤需要肿瘤血管系统提供氧气和营养物质，以支持其持续生长，并为转移扩散提供主要途径。在本研究中，TF级联靶向的策略，旨在破坏肿瘤血管的TF靶向HMME载药系统和PDT的组合。PDT是一种有前途的癌症治疗新模式，它利用肿瘤定位光敏剂与适当波长的光之间的相互作用来引起ROS诱导的细胞死亡。体外实验结果表明，EGFP-EGF 1蛋白修饰可显著促进TF过表达的BCECs对纳米粒的摄取。在体内多光谱荧光成像中，EGFP-EGF 1缀合的纳米颗粒显示出比非缀合的纳米颗粒在肿瘤组织中显著更高的积累。肿瘤组织切片进一步显示，EGFP-EGF 1缀合的纳米颗粒在肿瘤血管系统中显示出比非缀合的纳米颗粒显著更高的积累。体外研究表明PDT可增加BCECs TF表达。体内成像、离体成像和肿瘤组织切片显示PDT进一步促进EGFP-EGF 1-NP在肿瘤中的积聚。结果表明，PDT能促进EGFP-EGF 1修饰的PEG-PLGA纳米粒在肿瘤血管中的聚集。考虑到EGFP-EGF 1结合增强TF过表达内皮细胞对纳米颗粒的摄取，并且PDT增加内皮细胞TF表达。我们得出结论，PDT触发TF级联靶向效应。EGFP-EGF 1修饰与PDT联合应用对肿瘤血管具有正反馈靶向作用，有望成为肿瘤治疗的新方法。
Tumor requires tumor vasculature to supply oxygen and nutrients so as to support its continued growth, as well as provide a main route for metastatic spread. In this study, a TF-cascade-targeted strategy aiming to disrupt tumor blood vessels was developed by combination of TF-targeted HMME-loaded drug delivery system and PDT. PDT is a promising new modality in the treatment of cancers, which employs the interaction between a tumor-localizing photosensitizer and light of an appropriate wavelength to bring about ROS-induced cell death. In vitro results showed that protein EGFP-EGF1modification could significantly contribute to the uptake of nanoparticles by TF over-expressed BCECs. In vivo multispectral fluorescent imaging, the EGFP-EGF1 conjugated nanoparticles showed significantly higher accumulation in tumor tissues than non-conjugated ones. Tumor tissue slides further presented that EGFP-EGF1 conjugated nanoparticles showed significantly higher accumulation in tumor vasculature than non-conjugated ones. In vitro study demonstrated that PDT increased TF expression of BCECs. In vivo imaging, ex vivo imaging and tumor tissue slides showed that PDT further contribute EGFP-EGF1-NP accumulation in tumor. These promising results indicated that PDT enhanced EGFP-EGF1modified PEG-PLGA nanoparticle accumulation in tumor vaculature. Considering that EGFP-EGF1 conjugation enhanced nanoparticles uptake by TF over-expressed endothelium and PDT increased endothelium TF expression. We conclude that PDT triggered a TF cascade targeted effect. A combination of both EGFP-EGF1 modification and PDT provided a positive feed-back target effect to tumor vessels and might have a great potential for tumor therapy.