The Preparation And Biomedical Properties Of PH-sensitive Polymeric Micelle

Cancer has been one of the most threats in influencing human's health.More and more people were died of cancer. The therapy of cancer generally includes chemotherapy, operative treatment and radiotherapy. The common cure could kill most tumour cells but had significant side effects as well. So, how to improve the drug's targeting properity, the ability of drug controlled release and decrease injury to normal tissues has been a key point to the researchers.Bio-responsive nanoparticles responding to biological stimulations have been exploited to improve the biological efficacy for the diagnosis or therapy of human diseases. Among all of the biological stimulations, pH stimulation is the most studied. Based on the pH difference between tumor site and nomoal tissues, we did two studies.In the first part, we designed a three-arm polymer by several reactions from a original small molecule. The three-arm polymer includes three parts: hydrophilic chain segment (PEG), pH-sensitive segment and hydrophobic chain segment. Owing to the unique structure and the existence of pH-sensitive monomer C7A, the micelle we prepared had two features, that is the size of the micelle would get bigger (95 nm to 157 nrm)and the zeta potential would change from electric neutrality to positive charge (0 mV to 20 mV) when the pH changes from neutral to acidity. In the tumor microenviroment,cancer cells display a "reversed" pH gradient with a constitutively increased cytoplasmic pH and lowered extracelluar pH (pHe = 6.5-6.9). Due to the universal characteristic of cancer, our micelle can enhance the cell uptake and improve the accumulation of tumor.The second part, we introduced a tetrapeptide GFLG which can dissociate by cathepsin B at acidic condition by modifying the natural polymer chitson. We load the prodrug VE-PTX into chitosan to prepare nanoparticles and use the hyaluronic acid (HA) which can target CD44 overexpressing in tumor to attach to the surface of nanoparticles through electrostatic interaction. A series of experiments in cellular level indicated that the introduction of HA do improve the targeting performance. The nanopraticles played an important role in promoting drug realease and overcoming multidrug resistance.