The Study Of Protein-based Carrier System Loading Paclitaxel And Possible Mechanism Of A Near-infrared Dye Special Accumulation In Mice

Paclitaxel has an special therapeutic effect in treatment of kinds of cancer. It is used as the first-line treatment of non-small cell lung cancer, breast cancer, ovarian cancer and so on. So, Paclitaxel holds a large market share all around the word. As its almost insolubility in water, the development of safe and effective paclitaxel formulation draw much attention in the field ofresearch. Paclitaxel injection using Cremophor EL as its solubilizer on the market leads serious side effects, which brings great challenge in clinical. Nanotechnology shows great success in the Paclitaxel solubilization, and can be used to load paclitaxel to reduce its side effect and improve therapeutic effect.FDA approved AbraxaneTM as a novel PTX formulation in2005, and itachieved great success in the market.In this research, Pharmacodynamics and acute toxicity of PTX-HSA nanoparticles prepared following our lab patents were further evaluated in tumor-bearing mice and Beagle dogs respectively, In Pharmacodynamic experiment, our nanoparticles were injected into tumor-bearing mice at the same dose as AbraxaneTM. Tumor size was tested to compare their antitumor effect. In acute toxicity experiment, we divided PTX-HSA nanoparticles into three dose groups of high, medium and low, and compared the acute toxity with Paclitaxel injection. The results showed that the toxicity of PTX-HSA nanoparticles significantly lower than paclitaxel injection.To improve the "nano-platform" of protein carriers, we choose another protein, hemoglobin as a carrier to load paclitaxel and get the paclitaxel-loading hemoglobin nanoparticles. The novel nanoparticles were charaterized in terms of size, shape, Zata potential,spectroscopy. Results indicated that paclitaxel-loading hemoglobin nanoparticles may have further application prospects.A near-infrared fluorescent dye(IR780) was investigated in the last part of this research. IR780and three other similar compounds IR775, IR792, ICG were injected into nude mouse to observe their metabolism and distribution in nude mice. We found that IR780can accumulate in the testis and submandibular gland.