EGFP-EGF1 protein-conjugated PEG-PLA nanoparticles for tissue factor targeted drug delivery.
In a strategy for anti-thrombotic therapy, we have expressed EGFP-EGF1 fusion protein, in which EGF1 can bind with tissue factor (TF). EGFP has previously been widely used as a fluorescent protein marker. EGFP-EGF1 protein was thiolated and conjugated to the malemide covering on the pegylated nanoparticles (NP) to form the EGFP-EGF1-NP. The EGFP-EGF1-NP was characterized in terms of morphology, size and zeta potential. In vitro cell viability experiment confirmed that the biodegradable EGFP-EGF1-NP was safe. To evaluate the delivering ability of EGFP-EGF1-NP, a fluorochrome dye, Dir, was incorporated into the nanoparticle, and the loading capacity and release property of the particle were examined. In vitro results showed that the binding ability of EGFP-EGF1-NP with TF-expressing cells was significantly stronger than that of non-conjugated NP. In vivo multispectral fluorescent imaging demonstrated that EGFP-EGF1-NP had high specificity and sensitivity in targeting thrombi. Our study demonstrated that EGFP-EGF1-NP is a promising TF-targeting drug delivery system for thrombolytic treatment.
Mei
Heng
H
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, PR China.
Shi
Wei
W
Pang
Zhiqing
Z
Wang
Huafang
H
Lu
Weiyue
W
Jiang
Xinguo
X
Deng
Jun
J
Guo
Tao
T
Hu
Yu
Y
D000818:Animals; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D005167:Factor VII / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism*; D014018:Tissue Distribution
D004337:Drug Carriers; D011993:Recombinant Fusion Proteins; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols; D005167:Factor VII; D013925:Thromboplastin