Study On The Preparation And Biologic Application Of Novel Multi-functional Inorganic Semiconductor/polymer Composite Hydrogels

In recent years, photodynamic therapy (PDT) and sonodynamic therapy (SDT) are novel treatments that have high specificity, minimal invasiveness and good cosmetic outcome for cancer and certainnon-cancerous. Photosensitizers(sonosensitizers) is the most important part of PDT(SDT), the most commonly used photosensitizers (sonosensitizers) are porphyrin based molecules in PDT, these organic or organometallic dyes are, however, prone to photoinduced degradation and enzymatic degradation, which becomes problematic in PDT(SDT) treatments, and reduces the efficiency of the generation of singlet oxygen. With the development of nanotechnology, a new classes of inorganic photosensitizers brings a promise for the solution of these problems, semiconductor nanonmaterial were applied in the field of phototherapy of malignant cells, and have been regarded as the potential photosensitizing agents for PDT and SDT due to their excellent stable properties and unique toxic effect upon the excitation condition. However, the semiconductor nanonmaterial still have some drawbacks in the clinical use, such as insufficient selectivity and low efficiency resulted from lack of cell-specific accumulation of semiconductor nanonmaterial on cancer cells. Therefore, finding an appropriate method for reducing the flow of semiconductor nanonmaterial or even concentrate the semiconductor nanonmaterial in together to construct a localized PDT and SDT system is of great importance in the medical nanotechnology field,In the dissertation, we developed, a novel in situ polymerization of semiconductor nanonmaterial/polymer hybrid hydrogel system formed on the focus area for PDT and SDT. These new systems provide some new ideas and means for developing more effective antitumor methods. The main results can be summarized as follows:1. In this section, we developed novel in situ photopolymerization of Fe2O3/MB/PEGDA hybrid hydrogel formed on the tumour cells for PDT. In this process, Fe2O3colloidal particles were used as photoinitiator for the polymerization of PEGDA, MB was photosensitizer in this system to generate single oxygen(1O2). After irradiated by laser (λ=660nm), the precursor was rapidly converted into hydrogel on the surface of tumor cells, the hydrogel shell can prevent Fe2O3from fluxion to all over the body so that the normal cell was less damaged and the hydrogel may also shield the MB encapsulation in it from degradation into an inactive form thus with potentially much greater availability in PDT.2. In this section, we developed a novel in situ photopolymerization of TiO2/PEGDA hybrid hydrogel formed on the tumour cells for PDT. In this process, TiO2colloidal particles were used as both photosensitizer for antitumour and photoinitiator for the polymerization of PEGDA, the hydrogel precursor is incubated with the cells in lesion site, after irradiated by laser (λ=660nm) the precursor was rapidly converted into hydrogel on the surface of tumor cells, and synchronously cancer cell was killed by the singlet oxygen released from TiO2. The hydrogel shell can prevent TiO2from penetrating the normal tissue. Moreover, TiO2is a recyclable material in photochemistry, so this hydrogel system not only has the characteristics of simple preparation process, low cost, high curative effect and low dosage, but also may be used for long-course treatment in PDT.3. In this section, we developed a novel in situ sonopolymerization of hybrid hydrogel system for SDT. In this system, bovine hemoglobin was act as cross-inking agent, and riboflavin as model drug.TiO2colloidal particles were used as not only sonosensitizer for antitumour but also as initiator for the polymerization of PEGDA, in the condition of ultrasound radiation. The hydrogel shell can prevent TiO2from fluxion to all over the body so that the anticancer activities could be enhanced and normal cell was less damaged. Finally, riboflavin was taken as model drug for investigate the drug delivery capabilities of hydrogel, finding that under the simulated physiological conditions, the drug release time can last as long as216hours, so this hydrogel system may be not only has the characteristics of simple preparation process, low cost, high curative effect and low dosage, but also may be used combination with a chemotherapeutic agent to treat diseases.4. In this section, TiO2/chitosan/acrylic acid prepolymer was prepared by one-step method. This prepolymer is a smart material that can be rapidly converted to hydrogel when meeting phosphate buffer solution (pH7.4). Two halves taken from each of the original hydrogel were put together rapidly to have their freshly created fracture surfaces brought into contact,a single piece of hydrogel emerged quickly from the two halves without any stimulus or healing agent, so it has the self-healing performance. Finally, this hydrogel can be generated singlet oxygen under NIR irradiation, so it could be used for PDT, drug release and so on.