Synthesis Of Selenium-based Theranostic Core-shell Materials And Their Biological Application

Selenium is an essential trace element for the human body.Selenium supplementation can reduce the risk of cancer.Studies have also shown that selenium can inhibit the growth of cancer cells.However,the dose of Se between beneficial and toxic effects is narrow,so there are some limitations for the direct use of Se in clinical medicine and it is not so effective for short term ablation of solid tumors.Therefore,it is necessary to combine other treatment that can directly ablate the tumor.Photothermal therapy for tumor ablation is a non-invasive cancer treatment which can converts NIR light into heat by the PTT agent and effectively killing cancer cells.Combining PTT with Se can complement each other functionally and is a good tumor treatment.Besides,Se also shows good effect work with chemotherapeutic and PT agents because it can reduce the body's resistance to chemotherapeutics and improve its efficacy.Therefore,two new Se-based core-shell theranostics agents that integrate PTT and chemotherapy functions were designed.The main research contents are as follows:?1?To reduce the damage of ROS generated during PTT to normal cells surrounding the treated tumors,this paper designed a Se@Si O₂@Au-PEG/DOX NCs.First,the Au shell was coated by the gold seed growth method on the Se@Si O₂ NPs.Since the growth environment of the gold shell is weakly alkaline,Si O₂ was etched to generate Se@Si O₂@Au NPs with a cavity structure.In order to make Se@Si O₂@Au NPs more water-soluble and biocompatible,SH-PEG was used to modify the surface.Due to the large cavity structure,the loading rate of the anti-cancer drug Doxorubicin of Se@Si O₂@Au-PEG NPs is as high as 27.33%,and it can be controlled release in the weakly acidic tumor environment and NIR.The photothermal convert efficiency of Se@Si O₂@Au-PEG NPs is 45.1%,which is higher than most reported PTT agents.At the same time,both DOX and Se can play a role in killing tumors in concert with PTT effects.In vitro co-cultured cell experiments have shown that the excellent performance of Se in protecting normal cells during PTT.Also,Au has a strong X-ray attenuation ability and can be used as a good CT imaging agent to guide treatment.In vivo experiments proved that the synergistic effect of the composite material is more effective,and can ablate the tumor thoroughly and prevent its recurrence.Also,CCK-8,H&E staining,and the good growth status of mice also proved that the material is biosafety.Therefore,the diagnostic PTT NCs have great application potential.?2?To solve the obstacles caused by the hypoxic tumor environment during chemotherapy and PDT,and to enable the controlled release of DOX and Se in tumors,this paper introduced Mn O₂ into Se@Si O₂and designed a Se@Si O₂@Mn O₂-ICG/DOX NCs.Firstly,Mn O₂ was coated based on the porous Se@Si O₂ NPs.Since the porous structure of the material,it can be used to load photothermal materials?photosensitizers?ICG and DOX.The photothermal conversion efficiency of the material can up to 54.6%,so it can efficiently convert near-infrared light into heat to kill tumor cells for photothermal treatment.In addition,Se@Si O₂@Mn O₂ NPs can rapidly generate O₂ in the presence of H₂O₂of tumor environment to ameliorate the tumor hypoxia,and promote PDT and chemotherapy.At the same time,Mn O₂ can generate a large amount of ROS in the presence of H₂O₂ for CDT.Besides,it can be decomposed into Mn²⁺which with good water solubility and can be quickly discharged from the body as a T₁-weighted imaging agent to guide the treatment.Due to the sensitivity of Mn²⁺to the acidic conditions,high H₂O₂,and GSH of the tumor environment,it can cause rapid decomposition in the tumor environment and achieve the controlled release of Se and DOX.In vitro and in vivo experiments also proved that the biosafety of the material and the synergistic effect of PTT/PDT/CDT/chemotherapy are better than a single treatment.Therefore,the synthesized Se@Si O₂@Mn O₂-ICG/DOX NCs promote and complement each other in function,comprehensively solve the limitation of single tumor reagent,and have great potential in tumor theranostics.In summary,this paper designed two kinds of multifunctional NCs for synergistic PTT treatment based on Se NPs and made a comprehensive exploration in their characterization,performance,and anti-cancer effect.The results show that the above two composite material are based on Se NPs has excellent tumor diagnostic effect and have great potential in clinical application.