The Study Of The Modified Anticancer Drugs Based On Optical Molecular Imaging

Molecular imaging is the use of imaging method to display a specific level of tissue, cellular and subcellular level in vivo, and reveal its biological behavior in qualitative and quantitative aspects. Compared with conventional medical imaging, molecular imaging is "early detection, accurate diagnosis and clear view". The traditional diagnostic imagings(X-Ray, CT, MRI, ultrasound, etc.) display the final effect of molecular changes. And the structural changes that can be observed only for disease with anatomical changes. However molecular imaging can detect the abnormalities in cellular and molecular level before anatomic changes occur. Molecular imaging plays an important role in exploreing the occurrence and the development of the disease.Cancer is one of the major harmful diseases threatening human health and life, and the incidence is rising all over the world. Thus the anticancer drugs development and evaluation has been a hot issue. Using molecular imaging, through the design of specific imaging probes that can reveal the target change from in vitro to in vivo. The sensitive image analysis system improves the efficiency of drugs development.In this thesis, various imaging methods were combained to give a comprehensive assessment of the different antitumor drugs efficacy. The main contribution of this dissertation can be summarized as follows:1. Optical molecular imaging in DNA origami as an in vivo drug delivery vehicle for cancer therapy evaluation.Molecular imaging was carried to evaluate DNA origami modified Doxorubicin anti breast cancer efficacy in vivo. DOX as ordinary chemotherapydrug, its systemic side effects are known. DNA is high biocompatibility and chemical stability, we embedded DOX into an equilateral triangle DNA origami structure of side length 120 nm. Under the EPR effect influence, the drug distribution in the tumor region increased. The results comfirmed that the DNA origami modified DOX has better inhibition of tumor growth and less systemic toxicity than free DOX.2. Optical molecular imaging in Endostar anti-hepatoma angiogenesis efficacy assessment.In this study, bioluminescent molecule imaging(BLI), fluorescence molecular imaging(FMI), and micro-computed tomography(micro-CT) were combined to evaluate the Endostar inhibition of tumor angiogenesis in liver cancer from multi-angle. Molecular imaging was used to dynamic assess the Endostar tumor angiogenesis inhibition throughthe establishment of subcutaneous and orthotopic liver cancer tumor model. The traditional methods, such as biopsy was used to give the validation meanwhile. The results showed that in the period of drug administration, Endostar achieve a good effect of inhibiting tumor growth by inhibiting the growth of tumor angiogenesis.3. Optical molecular imaging in PLA coated nano Endostar in anti-cancer efficacy assessment.In this study, molecular imaging was applied to evaluate the PLA loading Endostar nanoparticles efficacy on inhibiting the growth of breast cancer. Through an adapted W/O/W double emulsion solvent evaporation method the polylactic acid(PLA) loading Endostar prepared in a diameter of about 140 nm nanoparticles. With the help of high permeability and retention effect(EPR) of solid tumors, drug passive transport in the tumor region was enhanced. The results showed that compared to free Endostar, PLA coated Endostar nanoparticles possessed better tumor growth inhibition during the treatment from in vitro to in vivo.4. Optical molecular imaging in GX1 peptied modified Endostar targeted therapy for anti-colorectal cancer evaluation.and tumor growth inhibition of colorectal cancer was assessed in vivo by molecular imaging. GX1(CGNSNPKSC) is a specific ligand which was screened by phage display to target tumor endothelium. Using this peptide to modify nano Endostatr to enhance the nanoparticle tumor region accumunation. The results indicated that compared with PLA loading Endostar nanoparticle, GX1 modified endostar nanopaticle exhibit better tumor convergence capability and tumor growth inhibition.