| Reactive oxygen species?ROS?play an important role in the growth and metabolism of tumors.The appropriate level of ROS in the cancer cells can promote cell proliferation and survival,but the high level of ROS will destroy DNA and proteins in the cells which will cause cell death.Therefore,treating cancer by increasing the levels of ROS in cancer cells is a very attractive and feasible strategy.Fenton reaction,H2O2 catalyzed by iron ions to produces highly toxic hydroxyl radicals?·OH?,is considered to be an effective method to increase the levels of ROS in cancer cells.It can be used to treat cancer alone or as an auxiliary way in combination therapy.Iron plays a catalytic role in the Fenton reaction process,and iron-based nanomaterials are safe and effective in clinical applications.Therefore,iron-based nanomaterials used to improve the level of ROS in cancer cells is significance.Based on the above considerations,we explore the route of iron promoting enhancement of reactive oxygen species in tumor and the preparation of corresponding nanoparticles and the research in killing cancers cells.The details of this work are as follows:1.Exploring the sensitizing effect of iron-based materials to hypothermiaPhotothermal therapy has become an important means of tumor treatment.When the temperature is 50°C above,it can effectively inhibit tumor growth,but this will cause damage to surrounding normal tissues.By contrast,the low-temperature photothermal therapy is critical toward the successful cancer treatment.In the process of low-temperature photothermal therapy,cancer cells can response to the hypothermia stress,which will cause an increase in ROS levels in cancer cells.This process may be accompanied by an increase in H2O2.Therefore,in this chapter,we set the cell incubator at different temperatures to simulate the photothermal therapy process,and then explore the sensitization of iron-containing materials to hypothermia.The experimental results showed that:?1?With the increase of temperature and incubation time,the viability of MCF-7 cells decreases significantly;?2?The apoptosis rate of MCF-7 cells is 17.19%with heating treatment?45°C?for 1 h.When the MCF-7 cells is treated with heating and iron-containing materials,the apoptosis rate of cells and the level of ROS is similar to that treated with heating alone.It may be due to that the low-temperature heating process promotes the production of intracellular ROS.However,the level of intracellular H2O2 does not increase or the amount of increase is low.So the introduction of iron ions is insufficient to increase the sensitivity of cells to hypothermia.2.Encapsulation of glucose oxidase in Fe?III?/tannic acid nanocomposites for effective tumor ablation via Fenton reactionIn previous chapter,we found that increasing the content of H2O2 in tumor cells is an important factor in improving the efficiency of Fenton reaction.Therefore,in this chapter,enhancing the efficiency of Fenton reaction by increasing the concentration of H2O2 based on the GOD catalyzing glucose is explorated.Based on this,GOD-FeIIITA nanoparticles are synthesized by one-step method.The catalytic ability and the degradation behavior of GOD-FeIIITA nanocomposites is investigated.Then the cytotoxicity of GOD-FeIIITA is evaluated by cell experiments and animal models.The experimental results show that:?1?The size of GOD-FeIIITA nanocomposites with good dispersibility is about 200 nm and the loading capacity of GOD is 8.1%;?2?FeIIITA nanocomposites shows higher catalytic activity than pure Fe2+in converting H2O2 to·OH by decolorization experiment of methylene blue,which indicating that FeIIITA can be used as an excellent Fenton reaction reagent;?3?GOD-FeIIITA nanocomposites are responsive to tumor acidic environment.Under the mildly acidic condition,GOD-FeIIITA nanocomposites can effectively catalyze glucose to produce·OH,but this process is substantially suppressed under the netural condition;?4?GOD-FeIIITA nanocomposites can effectively kill cancer cells by generation of large amounts of ROS and shows obvious tumor-suppression effect after intratumoral iniection.3.Preparation of Fe?III?/tannic acid coated organosilica with high drug loading and its application in cancer treatmentIn addition to the discussion above on the route of iron to promote ROS enhancement,next,the chemotherapy drug doxorubicin?DOX?as the representative is used to explore that the iron promote ROS production to enhance the anticancer effect of chemotherapy drugs.Based on this,in this chapter,mesoporous organosilica nanoparticles with high drug loading are selected as drug carriers.After adsorbing DOX,MONs-DOX@FeIIITA nanoparticles are synthesized by one-step method.DOX can activate nicotinamide adenine dinucleotide phosphate?NADPH?oxidase?NOXs?,producing O2·-.Then the superoxide dismutase can convert O2·-to H2O2.The highly toxic·OH is produced through the catalytic action of iron ions to enhance the anticancer effect of chemotherapy drugs.The experimental results show that:?1?the size of MONs-DOX@FeIIITA is about 50 nm and the loading capacity for DOX is 28.57%;?2?There is a synergistic effect between DOX and free iron ions.When the concentration of DOX and Fe3+is 10?g/mL and 100?g/mL,the apoptosis rate in DOX group and DOX+Fe3+group is 11.12%and 20.88%,respectively.;?3?Although MONs-DOX@FeIIITA shows a dose-dependent decrease of cell viability,the viability of MCF-7 cells incubated with DOX@FeIIITA is higher than that treated with free DOX,which is due to the low release rate of DOX from DOX@FeIIITA or the short incubation time.Due to the restriction of time,the further exploration of the performance of DOX@FeIIITA is completed by other members in laboratory. |
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