| Traditional cancer treatments including chemotherapy, radiotherapy and surgical treatment, and chemotherapy is most widely used. However, due to the side effects of chemotherapy drugs and drug resistance, the effect of chemotherapy is unsatisfied, also patients endure great pain during treatment. The main reason for this phenomenon is that chemotherapy drugs do not have ability of targeting, to kill cancer cells but also damage normal cells. Currently, tumor targeted drug delivery to cancer treatment has become a hot research field.In addition to improving the traditional methods of treatment, the development of new methods of treatment is to improve cancer treatment success rate of a way. Photothermal therapy(PTT), a new minimally invasive tumor treatment technology developed in recent years is considered the most promising treatment methods bait replace traditional treatment has caused widely concern. During treatment, the tumor area in the near-infrared radiation in advance into the tumor tissue photothermal agents photothermal absorption is converted into heat causing local heat, burning the tumor tissue, to designated treatment tumor effect, significantly reduced during treatment systemic toxicity. Photothermal agents in the treatment play a crucial role in the current noble metal nano-materials because of its excellent optical properties by researchers conducted in-depth research, mainly in gold, silver and palladium nano-materials research, though fruitful However, other precious metals did not study the nature of light and heat, which limits the photothermal therapy in the development of materials for the diversity of noble metal nanoparticles.Based on the above background, this paper designed and synthesized a series of studies of nanoparticles for targeted delivery of chemotherapy drugs load and the effect of light and heat on the basis of previous work, it aims to search for new drug delivery systems and new photothermal agents. The full paper is divided into four chapters.The chapter 1 is the introduction, which briefly describes the treatment of tumors and the concept of targeted drug delivery problems, but focuses on the mesoporous silica used in the drug system. Then introduced the principle of the status quo and photothermal therapy, the noble metal nano-materials as photothermal agents are classified Introduction. Finally expounds the purpose and significance of this subject.In chapter 2, to mesoporous silica synthesized by oxidizing a dual core carrier chemotherapy drug doxorubicin(Dox) and the reduction of siRNA-responsive drug delivery systems(MSNs-SS-siRNA @ Dox). Dox encapsulated in Mesoporous, siRNA connected by disulfide bonds showed that the mesoporous silica mesoporous played blocking role. We first examine the nature of drug delivery systems in simulation experiments and intracellular drug release results show the drug delivery systems exhibit controlled release properties and can significantly increase the content of the drug in the cell under the effect of reducing agent. Secondly, the gene silencing efficiency MSNs-SS-siRNA @ Dox have also been detected, it showed target gene expression was significantly down-regulated in the delivery system under the action. Finally, in vivo imaging technique to study the ability of MSNs-SS-siRNA @ Dox in mice in vivo targeting of tumor tissue, Dox by drug delivery systems may be more likely to concentrate in the tumor region, it reflects the apparent targeting. In vivo anti-tumor effect proved MSNs-SS-siRNA @ Dox Dox system to reduce systemic toxicity while significantly improving the anti-cancer effect.In chapter 3, for the first time to study the ruthenium nanoparticles(RuNPs) photothermal activity. The results showed that in the near infrared region RuNPs significant and broad absorption, the light-heat conversion efficiency reached 53.2%. Under 808 nm laser irradiation at a concentration of 10 μg ml-1 RuNPs of aqueous dispersions can be within 10 min temperature 31.3 ℃, showed RuNPs with good photothermal effect. In order to increase the absorption cell RuNPs We nanoparticles surface modification on the transferrin(Tf-RuNPs), it showed that Tf modification significantly improved the A549 cells to nanoparticle absorption capacity, at the same time does not affect the photothermal properties RuNPs. Finally, the anti-tumor cells in vitro and in vivo experiments proved Tf-RuNPs and in RuNPs have good biocompatibility while under laser irradiation can effectively kill cells, especially Tf-RuNPs 12 days to completely remove the tumor cells. With good light RuNPs thermal properties and biocompatibility, Tf-RuNPs can be used as a photothermal agents for photothermal cancer therapy.In chapter 4, we first synthesized a flower-like ruthenium nanoparticles(FRu), and the development of its excellent thermal properties of light. Compared with ordinary ruthenium nanoparticles(SRu), FRu due to the higher absorption in the near infrared region and thus better photothermal effect. In addition, we detected two ruthenium nanoparticles to produce reactive oxygen species(ROS) capacity, and the results show SRu FRu at near-infrared laser have the ability to produce ROS, cell experiments yielded similar results, which may be beneficial anti-tumor effect. Although the two kinds of cells to absorb the ruthenium nanoparticles and no significant differences, but the ability to kill cells under laser irradiation FRu significantly stronger than SRu. Finally, in vivo tumor-bearing mice treated group showed FRu interval laser irradiation of tumor tissue completely cleared within 14 days, a good performance in vivo anti-tumor effect of light and heat therapy. |
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