| Nowadays,cancer is one of the life-threatening diseases.Surgery,chemotherapy and radiation therapy are major treatment methods in clinical,which have certain limitations,for example,surgery is often unable to complete resection of the tumor cells.Chemotherapy and radiation therapy damage the normal cells,due to lack of targeting.In recent years,with the development of nanotechnology,the integration of a variety of therapeutic methods not only greatly improve the efficiency of tumor treatment,but also reduce the dosage of drugs,reduce side effects.This combination therapy has become one of the hot spots.Therefore,we functional design selenium and tellurium nanoparticles by simple operation to achieve chemo-gene/ chemophotohermal combination cancer therapy and then to explore its antitumor activity.The main results are as follows:1.Targeted selenium nanoparticles loading doxorubicin and si RNA to achieve chemo-gene combination therapy for glioblastoma.Selenium nanoparticles(Se NPs)are a good carrier for anticancer drugs because of their good biocompatibility and low toxicity.In this study,we designed and prepared a novel nanosystem(Se-DOX-PAMAM-RGD-si RNA).That is,RGD modified PAMAM decorated selenium as payload of dox and si RNA.A series of chemical characterization of this nanosystem and its antitumor activity against glioma were investigated.The nanosystem exhibited uniform particles distribution and remained stable in water and FBS solutions in a long time.The results of IR,Zeta and agarose gel electrophoresis showed that the nanoparticles were synthesized successfully.Gene silencing efficiency of Se-DOX-PAMAM-RGD-si RNA was found significantly higher and faster than lipofectamine2000@si RNA by compared both intracellular fluorescent intensity of si RNA and Q-PCR assays.DOX loaded the nanosystem exhibited controlled-released behaviors and showed facilitated released in PH 5.3 circumstances.As targeting ligand,RGD surface decoration significantly enhanced the cellular uptake of Se-Dox-PAMAM-RGD-si RNA and increased the selectivity between normal and cancer cells.And then we established the blood-brain barrier(BBB)model to explore the ability of the nanosystem to penetrate BBB,which showed that the nanosystem effectively penetrate the BBB,and absorbed by U251 cells.In addition,we use the tumor spheroids in vitro to simulation solid tumors in vivo and explore the antitumor activity of nanoparticles,the results show that the permeability of Se-DOX-PAMAM-RGD-si RNA on tumor spheroids than single Se-DOX nanoparticles.In a word,these results indicated that the synthesized se nanoparticles had a certain targeting and could inhibit the proliferation of glioma cells in the combination of chemotherapy and gene therapy.2.PTW modified tellurium nanorods to achieve simultaneous chemophotohermal combination cancer therapy.In this study,because of the surface modification of polysaccharide protein complex(PTW),this nanorods showed good stability,and keeps homogeneous solution more than 80 days,and had good blood compatibility.Cytotoxicity assay showed that due to the modification of PTW,PTW-Te NRs not only exerted extensive anticancer activities on different type of tumor cells but improved the selectivity between tumor cells and normal cells too.Thermal experiment in vitro shows tellurium nanorods have good photothermal conversion efficiency,could quickly convert light into heat under laser irradiation.tumor ablation studies in vivo also demonstrated high healing ability of mice treated with PTW-Te NRs under irradiation by laser at 808 nm.In addition,histological assays(H&E)showed that photothermal treatment of PTW-Te NRs did not caused obvious damage to normal organs of mice.These results indicate that the synthesized nanorods have good antitumor activity under the combined action of photothermal therapy and chemotherapy.Taken together,we modified selenium /tellurium nanoparticles functionally to achieve combination of chemotherapy and gene therapy / photothermal therapy. |
PDF Full Text Request