title: A tissue factor-cascade-targeted strategy to tumor vasculature: a combination of EGFP-EGF1 conjugation nanoparticles with photodynamic therapy.
abstract: 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.
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China.|Targeted Biotherapy Key Laboratory of Ministry of Education, Wuhan, Hubei, China.
authors: Wei
authors: W
authors: Shi
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China.|Targeted Biotherapy Key Laboratory of Ministry of Education, Wuhan, Hubei, China.
authors: Yanxue
authors: Y
authors: Yin
authors: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China.
authors: Yao
authors: Y
authors: Wang
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China.|Targeted Biotherapy Key Laboratory of Ministry of Education, Wuhan, Hubei, China.
authors: Bo
authors: B
authors: Zhang
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China.|Targeted Biotherapy Key Laboratory of Ministry of Education, Wuhan, Hubei, China.
authors: Pei
authors: P
authors: Tan
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China.|Targeted Biotherapy Key Laboratory of Ministry of Education, Wuhan, Hubei, China.
authors: Ting
authors: T
authors: Jiang
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China.|Targeted Biotherapy Key Laboratory of Ministry of Education, Wuhan, Hubei, China.
authors: Heng
authors: H
authors: Mei
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China.|Targeted Biotherapy Key Laboratory of Ministry of Education, Wuhan, Hubei, China.
authors: Jun
authors: J
authors: Deng
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China.|Targeted Biotherapy Key Laboratory of Ministry of Education, Wuhan, Hubei, China.
authors: Huafang
authors: H
authors: Wang
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China.|Targeted Biotherapy Key Laboratory of Ministry of Education, Wuhan, Hubei, China.
authors: Tao
authors: T
authors: Guo
authors: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China.
authors: Zhiqing
authors: Z
authors: Pang
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China.|Targeted Biotherapy Key Laboratory of Ministry of Education, Wuhan, Hubei, China.
authors: Yu
authors: Y
authors: Hu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000378:metabolism; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D051379:Mice; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D061848:Optical Imaging / Q000379:methods; D020653:Peptide Elongation Factor G / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; C441680:GFM1 protein, human; D024101:Mitochondrial Proteins; D020653:Peptide Elongation Factor G; D017319:Photosensitizing Agents; D011091:Polyesters; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; C485184:enhanced green fluorescent protein; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols
keywords: EGFP-EGF1; TF-cascade-targeted drug delivery system; photodynamic therapy; tissue factor