| Cancers have become one of the major diseases threatening human health. At present, clinical treatment for cancer mainly including surgical removal method, chemotherapy and radiotherapy. However, these above therapies have some limitations. Taking chemotherapy for example, as a broad-spectrum drug, anthracycline-based chemotherapy drug doxorubicinn has been proved to present seriously toxic effects. It can cause irreversible cardiomyopathy, hair loss, and bone marrow suppression and so on when used for a long period of time. Doxorubicin analogues, combination therapy and medicinal new drug delivery system have been developed in order to reduce the toxicity of doxorubicin and improve treatment effect.Photothermal therapy (PTT) as a minimally invasive cancer treatment technology has attracted more and more attention. The photoabsorbing agents can generate heat from optical energy when the photoabsorbing agents enter into the cancer tissue and plus a laser irradiation. In the same near-infrared (NIR) light irradiation, the temperature at tumor site is higher than that in normal tissue. In addition, the cancer cells are sensitive to temperature, leading to thermal ablation of cancer cells and the subsequent cell death. With the innovation of technology, nanomaterials play indispensable roles in drug development and delivery because of its unique properties. Photothermal therapy with nanomaterials as the carrier has attracted much attention. There are many researches on gold nanomaterials, carbon nanomaterials, and copper chalcogenides and so on.Multimodal combination methods for the treatments of cancers can achieve good treatment effect and it has been researched extensively in recent years. Chemotherapy and combined with thermal properties of nanomaterials is conducive to overcome the side effects of traditional anti-cancer drugs on normal tissue. In addition, PTT agents of nanomaterial can increase cancer cells temperature and will kill tumor cells. So it can attain the synergistic therapy. However, a single kind of nanomaterial is difficult along with high drug loading and photothermal properties. Pure mesoporous silica (MSN) has higher drug loading and easy modification, but it does not have photothermal property. Copper chalcogenides with LSPR absorption has some disadvantages, such as poor targeting, difficult modification and drug loading. This two kinds of nanomaterial can only play a role when used alone. In view of the above problem, we prepared two kinds of composite nanomaterials for drug delivery based on the reduced graphene oxide (rGO) and MSN or copper chalcogenides. Thus this composite nanomaterials with two unique properties of nanomaterials. We did research about the drug release behavior, and analysis of drug delivery and treatment by confocal fluorescence imaging. The research contents include the following two parts:(1) DOX@MSN@rGO-FA drug delivery system:We developed a novel versatile system for cancer cells with the combination of chemotherapy and phototherapy by using MSN and rGO. We studied the UV-vis spectrum, photothermal effect, pH release behaviors, cell uptake imaging, cell toxicity, and chemotherapy and photothermal therapy effect and so on systematically. The unique advantages of such multifunctional nanoparticles include:1) Confocal fluorescence imaging analysis:the DOX and photothermal agent can be specifically delivered into cancer cells via a receptor-mediated endocytosis pathway owing to FA target that can minimize nonspecific toxicity.2) The drug cumulative release rate is about three times in acidic environment as many neutral condition under NIR irradiation. Because the rGO nanosheets as the gatekeeper can detach from the silica and expose the pores of mesoporous silica in the acidic environment. The temperature of solution rise after NIR irradiation that can accelerate the release of DOX. This reduces the side effects of drugs on normal cells.3) The rGO can effectively absorb and convert NIR light to heat upon irradiation with NIR laser. When the multifunctional nanoplatform enters into cancer cells followed by NIR light irradiation, both chemotherapy and photothermal therapy can be activated and confocal fluorescence imaging can directly observed this effect.(2) Cu2-xSe@rGO-FA-DOX drug delivery system:The monodispersed copper selenide nanoparticles (Cu2-xSeNPS) was gained by simple room temperature synthesis method and it has a strong thermal conversion efficiency. Composite nanomaterials with a variety of functions formed when adding the rGO to the Cu2-xSeNPS solution. On the one hand, thermal performance of Cu2-xSeNPS is strengthen. Photothermal heating curves present that the temperature of composite nanomaterials increase faster than the same concentration of Cu2-xSeNPs. On the other hand, Cu2-xSeNPS have new functions. For example, composite nanomaterials are easy to couple with folate and can target to cancer cells. The confocal fluorescence imaging can be employed to observe the behavior of composite nanomaterials targeted cancer cells. In addition, rGO can load drugs and release them under acid condition. The performance above can reduce the side effects supply the chemotherapy and photothermal therapy effect at the same time.In conclusion, novel composite nanomaterials drug delivery system based on rGO with MSN or Cu2-xSeNPS have multiple functions. The composite nanomaterials target to cancer cell due to folate and drug release behavior is temperature dependent and acid sensitive. Thus, it can reduce the side effects of chemotherapy drugs on normal cells, realizing synergistic therapy combine chemotherapy and photothemal therapy. All the results showed that the functional composite nanomaterials showing a potential application prospect. |
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