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Synthesis Of Au@SiO2 Nanocomposite Materials And Their Photothermal Therapy Applications In Liver Cancer

Posted on:2012-08-08Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z S LiangFull Text:PDF
GTID:1101330335966028Subject:Polymer Chemistry and Physics
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Cancer is one of fatal diseases worldwide. According to the report of World Health Organization (WHO), there are 10 million cancer-related disease diagnosed and 7.4 million people (13 percent of the total) were dead annually all over the world. Therefore, cancer is considered the "health killer" to human in 21 century. Among these, lung cancer, stomach cancer, colon cancer and liver cancer are mainly responsable for the cancer-related death. Recently, cancer therapies are mostly focused on chemotherapy, radiotherapy and surgery method. However, all these methods have some limitations and lead to obvious side effects. For example, chemotherapy tends to fail beacuse of their high toxicity and patients can not be tolerant to a long-time therapy, and surgical operation will wound tissue and always has a high risk. Thus, the non-invade therapeutic methods which can selectively kill cancer tissue but do no harm to normal tissue are needed urgently. Recently, with the development of nanotechnology, photothermal therapy which is one of physiotherapies based on nanomaterials has attracted extensive attentions. Optical energy can be absorbed by these special nanomaterials and transfered to thermal energy to heat the lesion and kill the cancer cells. These nanomaterials include gold nanoshells, gold nanorods and so on.Gold nanoshell (GNs) is a sphere nanomaterial with the size of 100-200 nm in diameter, which consists of a spherical dielectric nanoparticle core (normally silica) coated by a thin gold layer (Au@SiO2). It was firstly synthesized by Halas group of Rice University in 1998 and had attracted many attentions because of its excellent optical properties. The intense optical absorption and scattering properties of gold nanoshells can easily be made to span from 700 to 1100 nm in near infrared region (NIR) by adjusting the ratio of the shell thickness to the core radius. Near infrared light can maximally permeate through blood and tissues and reach the deep tissue because of "tissue window" effect, which led to a little detriment to the healthy tissue. Thus it is an ideal way to utilize the NIR laser as the energy source for photothermal cancer therapy. GNs can absorb and convert the NIR radiation into heat efficiently, and it would remain a relatively stable core-shell structure at therapeutic temperature (43-63℃). Therefore, as new mediators of photothermal cancer therapy, GNs show a great potential in the application of cancer therapy. GNs are promising in other biomedical fields as well, such as cell imaging, medical diagnosis and drug delivery.In the application of GNs in biomedical field, they were preferentially accumulated at tumor sites due to the EPR (enhanced permeability and retention effect) effect which lead to a passive targeting to tumor. But it is hard to achieve the optimum therapy effect depending on the passive targeting method only. In spite of the great achievements of chemotherapy drugs obtained in clinical cancer therapy, it was found that only a small fraction of the administered dose of anti-cancer drug (such as doxorubicin) reaches the tumor, while the most rest of the drug is distributed throughout the body. This causes an undesirable damage to non-cancerous tissue.In this thesis, firstly, the applications of gold nanoshells (GNs) and their progress of study were reviewed (Chapter One). In the following section, gold nanoshells with absorption peak at about 800 nm in near infrared region (NIR) were fabricated. And some important parameters that affect the growth of gold nanoshells and the possible mechanism have been studied in detail (Chaper Two). Based on these studies, a series of new nanocomposite materials (DMSA@GNs, mPEG@GNs, A54@GNs, Dox@GNs) derivated from gold nanoshells were synthesized through surface modification. The stability, biocompatibility, optical properties of these functionalized nanoparticles was investigated by UV-vis spectra, TEM and DLS. Furthermore, the cellular uptake ability of DMSA@GNs was studied carefully (Chaper There). The therapic efficiency to cancers is directly related to the circulation time in blood and the internalized number of GNs. So in the next section, some further chemistry modifications were introduced to the surfaces of GNs through polyethylene glycol (PEG) and targeting peptide (Chaper Four and Five). The introduction of PEG was expected to prolong the circulation time of GNs in blood and the peptide (named A54, AGKGTPSLETTP) can enhance the targeting ability of GNs to liver cancer cells. In vitro experiments, the cellular uptake, the physiological stability, the targeting ability to liver cancer cells and the photothermal therapy of A54@GNs were studied. In the last section, doxorubicins (Dox) were conjugated to nanocomposite materials to obtain a thermal-combined chemotherapy of these nanocomposites to liver cancer (Chaper Six). The series of experiments demonstrated that all these functionalized GNs showed a good ability to convert NIR light and kill the cancer cells and enhanced the chemotherapy efficiency. These nanocomposite materials present an excellent optical property and are very promising in the application of the therapy of liver cancers.
Keywords/Search Tags:Gold nanoshells, Preparation, NIR Light, Liver cancer, Photothermal therapy
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