Clinical Research Papers:
A tissue factor-cascade-targeted strategy to tumor vasculature: a combination of EGFP-EGF1 conjugation nanoparticles with photodynamic therapy
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Wei Shi1,2,*, Yanxue Yin1,2,*, Yao Wang3,*, Bo Zhang1,2, Pei Tan1,2, Ting Jiang1,2, Heng Mei1,2, Jun Deng1,2, Huafang Wang1,2, Tao Guo1,2, Zhiqing Pang3 and Yu Hu1,2
1 Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China
2 Targeted Biotherapy Key Laboratory of Ministry of Education, Wuhan, Hubei, China
3 Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China
4 Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China
* These authors have contributed equally to this work
Tao Guo, email:
Zhiqing Pang, email:
Yu Hu, email:
Keywords: EGFP-EGF1, tissue factor, TF-cascade-targeted drug delivery system, photodynamic therapy
Received: July 18, 2016 Accepted: October 22, 2016 Published: October 26, 2016
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.
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