The Construction Of NIR/pH-Triggered Multi-Modal Cooperation System Under The Multiple Responses

With the rapid development of nanotechnology,"nano-delivered medicine medical treatment" has opened up a new path in the treatment of anti-tumor applications.In order to achieve active targeting of the tumor,at the same time trigger drug release to achieve synergistic treatment of the tumor effect.This paper uses the characteristics of tumor microenvironment-low pH,high glutathione concentration,poor heat resistance and consumption of a large amount of glucose,the following four functional nanocarrier platforms are specifically designed:1.Based on the characteristics of high glutathione concentration and poor heat resistance in the slightly acidic environment of tumor,a photothermal/chemotherapeutic system with double response of glutathione and acid was designed（Au@SiO₂@MnO₂/5-Fu@PDA）.The system consists of Au nanoparticles,SiO₂ shell layer,MnO₂ coating layer,polydopamine（PDA）and chemotherapy drugs（5-Fu）.Among them,the role of Au and PDA is to use nearinfrared（NIR）laser irradiation to convert light energy into heat,thereby triggering tumor thermal ablation.Coating MnO₂ can not only increase the specific surface area of the carrier but also overcome the problem of hypoxia.The experimental results show that the system has good photothermal conversion rate（?=34.4%）and photothermal stability.Cytotoxicity experiments show that the system has good biocompatibility and excellent anti-tumor efficacy,and the combination of chemotherapy and photothermal therapy is better than monotherapy.2.According to the characteristics of poor heat resistance and slightly acid environment in tumor microenvironment,a photothermal/chemotherapy research system with acid response Au@Pt@PEI/5-Fu@PDA was designed.The system uses a one-pot template method to synthesize Au@Pt NPs,and then modified with PEI to improve their biocompatibility and physiological stability.The PDA is now used as a "gatekeeper" to encapsulate the outer layer.The performance of the nanocomposite Au@Pt@PEI/5-Fu@PDA was verified by drug capture rate,drug sustained release,photothermal performance and MTS toxicity experiments.The experimental results showed that the system had a high drug loading rate（29.4%）,the highest drug release rate in acidic environment（ΔY=0.35）,a high photothermal conversion ability（47.9%）and a good anti-tumor effect（81%）in multi-mode synergistic treatment.3.In this chapter,according to the characteristics of the tumor’s acidic environment,poor heat resistance and high glutathione concentration,a photothermal/chemotherapy treatment system based on MnO₂ is designed under the dual response of acid and glutathione.The system uses honeycomb MnO₂ with a unique morphology as a drug carrier.The porous structure provides a physical threedimensional space.In addition,the CuS and PDA coating layer can show strong absorption capacity in the near-infrared region.The dual photothermal therapy （PTT）of CuS and PDA can greatly improve the photothermal therapy effect and effectively inhibit tumor growth.The combined use of PTT and the anti-cancer drug 5-Fu can further inhibit the growth of tumors in the body.The experimental results showed that the system had a high drug loading rate（61.8%）,the highest drug release rate（ΔY=0.3599）,a higher photothermal conversion capacity（32.4%）and a better mortality rate（85.44%）for synergistic treatment.4.Based on the characteristics of high glutathione concentration,large amount of glucose consumption and poor heat resistance in the micro-acidic environment of tumor,a photothermal/chemotherapy/starvation therapy system CuS@MnO₂/5-Fu@PDA/GOD with hollow CuS nanostructure as carrier was designed.This article adopts the method of layer-by-layer coating to synthesize this nanocomposite treatment system,hollow CuS nanoparticles as the core,it can respond quickly to near-infrared radiation and light-to-heat conversion capabilities,the external MnO₂ coating can provide a larger specific surface area,providing more space for the loading of the late chemotherapy drug 5-Fu.Then use PDA to encapsulate the outer layer as a "gatekeeper",and finally use glucose oxidase（GOD）as the outermost passive targeting agent for starvation treatment.The experimental results show that the system has a high drug loading rate（46.2%）and a high photothermal conversion ability（48.9%）,and the synergy therapy has good anti-tumor properties（78.5%）.