Construction Of Tellurium Nanorod-based Complexes And Their Application In Tumor Therapy

In recent years,nanotechnology has been widely used in the biomedicine.Nanomaterials are increasingly favored by researchers due to their versatility,facile preparation,and stable properties.It is important to continuously explore the application of new nanomaterials in biomedicine.Especially in the diagnosis and treatment of tumors,nanomaterials provide a powerful tool for accurate diagnosis and efficient treatment of tumors.Chalcogen-based nanomaterials were widely used in the occurrence,development,diagnosis,and treatment of tumors.However,there are few studies and applications of tellurium in tumor diagnosis and treatment.In this thesis,tellurium nanorods（Te NRs）were synthesized by hydrothermal methods,mineralization,and a series of integrated diagnostic and therapeutic nanoplatforms were constructed based on Te NRs for multimodal imaging and combined therapy of tumors.The main research contents are as follows:（1）Polypeptide-based Te NRs were in situ synthesized and used for combined photothermal and sonodynamic therapy of tumors.The triblock polypeptide PC₁₀ARGD nanogels were designed by genetic engineering technology.PC₁₀ARGD contains two coil-coil domains P and A,a random coil domain C₁₀,and a targeting sequence RGD.PC₁₀ARGD can form nanogel at low concentrations.Using PC₁₀ARGD as a ligand and a sterically confined nanoreactor,the tellurium nanorods（P-Te NRs）with uniform size and high biocompatibility were in situ mineralized and synthesized.The synthesized P-Te NRs have good uniform distribution and stability in water,PBS,and cell culture medium.P-Te NRs exhibited excellent photothermal conversion performance,and its photothermal conversion efficiency（38.9%）was higher than that of some common nanomaterials,such as copper sulfide nanoparticles（28.8%）and gold nanorods（22%）.Furthermore,P-Te NRs can efficiently generate reactive oxygen species（ROS）under ultrasonic excitation.The results of in vitro anti-tumor experiments showed that the cell survival rate of 4T1 cells was reduced to 12.4%after incubation with P-Te NRs for 4 hours and treatment under laser and ultrasonic stimulation,which was significantly lower than that with single photothermal（55%）or sonodynamic therapy（58%）.The in vivo anti-tumor experiments also showed that the P-Te NRs possessed good photothermal and sonodynamic therapy effect for 4T1 tumors.These works broaden the avenues for the application of tellurium in the biomedical field.（2）Although previous work has synthesized tellurium nanomaterials for tumor therapy,the lacks of imaging guidance and targeting capabilities of nanomaterials were bound to limit its application.Therefore,A biomimetic composite nanoprobe of Ag₂S QDs and inorganic nanoprodrug Te NRs camouflaged by cancer cell membranes was prepared in this chapter.Ag₂S QDs have NIR-II fluorescence imaging and photothermal conversion capability,and their fluorescence emission wavelength（～1050 nm）was located in the absorption wavelength range（200～1300 nm）of Te NRs.Ag₂S QDs and Te NRs were simultaneously loaded in the PC₁₀ARGD nanogels,and the fluorescence of Ag₂S QDs was quenched by Te NRs according to fluorescence resonance energy transfer.The cancer cell membrane endowed the nanoprobe with homologous targeting ability and immune evasion ability and greatly improved the biocompatibility of the nanoprobe.When the probes were specifically targeted to the tumor sites by intravenous injection,Te NRs in the composite probes were dissolved by high levels of H₂O₂ at the tumor site to generate toxic ions Te O₆^6-,which can be used as chemotherapeutic drugs.At the same time,the fluorescence of Ag₂S QDs was lit up for fluorescence imaging-guided tumor photothermal therapy.Experimental results showed that chemotherapy reduced mitochondrial activity,reduced ATP content in cells by 3.79 times,and further promoted the mild photothermal effect of Ag₂S QDs.The temperature increase generated by photothermal therapy in turn promoted the decomposition of Te NRs at the tumor site,resulting in a good synergistic effect between chemotherapy and photothermal therapy.Synergistic photothermal therapy and chemotherapy reduced drug dosage and toxic side effects on normal cells and tissues.This tumor microenvironment stimuli-responsive multifunctional integrated nanoprobe provides a new strategy for synergistic tumor therapy guided by NIR-II fluorescence imaging.（3）Studies have shown that chronic inflammation caused by photothermal therapy will hinder the efficacy of photothermal therapy and promote tumor recurrence.The use of the intrinsic antioxidant properties of tellurium nanomaterials to alleviate the inflammatory state induced by photothermal therapy is a further development of the application of tellurium in antitumor.Therefore,A Pt/Te binary heterostructure nanorod with high photothermal conversion efficiency and anti-inflammatory ability was designed and synthesized for photoacoustic imaging-guided tumor photothermal therapy and inflammation elimination in this chapter.The photothermal conversion efficiency of the Pt/Te nanoprobe was as high as 51.84%,which was significantly higher than that of single Pt and Te nanomaterials（～30%）.The high photothermal conversion efficiency was attributed to the unique localized surface plasmon resonance and increased electron transport pathways of the metals and semiconductors composing the nanoprobes.In vitro experiments showed that the intrinsic antioxidant capacity of the nanoprobe could effectively eliminate inflammation-related factors（TNF-α,IL-6,and IL-1β）and ROS.The encapsulation of the cancer cell membrane endowed the nanoprobe with better biocompatibility and homologous targeting ability.After intravenous injection of the probe into 4T1 tumor-bearing mice for 8 hours,the photoacoustic signal at the tumor site was significantly enhanced,which provided a strong guarantee for precise tumor treatment.In vivo experiments showed that 4T1 tumor growth was effectively abolished after performing a single 808 nm laser irradiation for 8 minutes.At the same time,the inflammatory state caused by hyperthermia at the tumor site was slowed down,the photothermal treatment effect was improved,and the tumor recurrence rate was reduced.This binary heterostructure of metals and semiconductors provided a new model for safer and more effective photothermal therapy of tumors.In summary,we explored a series of multifunctional nanomaterials based on Te NRs,which have been successfully applied to imaging-guided tumor therapy,and provided a strong basis for the use of tellurium nanomaterials in the diagnosis and treatment of tumors.