Bifunctional Tellurium Nanodots For Photo-induced Synergistic Tumor Ablation

In recent years,photothermal therapy(PTT)and photodynamic therapy(PDT)for photo-induced tumor ablation have attracted tremendous attentions over the world.Light-absorbing nanoagents with tumor-targeted ability can convert light to heat and produce reactive oxygen species(ROS)under near-infrared light irradiation,and then could kill cancer cells through the local temperature elevation(42 ~oC above)and toxic ROS.Therefore,PTT and PDT are considered to be promisingstrategies for cancer treatment due to the advantages such as high efficiency,minimal invasion,and low side toxicity.With the development of nanotechnology,nanomaterials for cancer therapy have become a focus of this field.At present,a variety of nanomaterials with near infrared light absorption properties have been reported for successful tumor photothermal therapy and photodynamic therapy,including gold nanomaterials,carbon nanomaterials,near-infrared fluorescent dye micelles and so on.However,single-component nanoparticles simultaneously achieve both photothermal and photodynamic synergistic therapy remains to be explored.Elemental tellurium(Te),as a chalcogenide element,has good photoconductivity,catalytic activity,piezoelectricity,and thermoelectricity,thus widely used in the field of electronics and optoelectronics.However,Te has been explored with limited success in its biomedical use,and thus a tremendous challenge still exists in the exploration of Te nanoparticles as an effective anticancer agent.Here,we introduce bifunctional Te nanodots with well-defined nanostructure as an effective anticancer agent for photo-induced cancer therapy with tumor ablation,which is accomplished using hollow albumin nanocages as nanoreactor.These nanodots can produce both effective photothermal conversion and generate reactive oxygen species(ROS)under near-infrared(NIR)light irradiation,thereby triggering the potent in vivo hyperthermia and simultaneous PDT at tumors.These investigations are shown as follows:Chapter 1.This chapter briefly introduces the present situation of malignant tumor and its treatment,systemically summarizes the research background of PTT/PDT and the nanomaterials for PTT/PDT,and then elucidates the objective and research content of this thesis.Chapter 2.Te-NDs with large absorption in the near infrared region were prepared and their structures and physicochemical properties were characterized.The average particle size of Te-NDs is 5.9±0.5 nm,and Te-NDsshowgood photostability and physical and chemical stability.Te-NDs can produce both heat and ROS under near infrared light irradiation,indicatingtheir further application in photothermal and photodynamic synergistic therapy.Chapter 3.In vitro cell experiments showed that Te-NDs were ingested into cells through a clathrin-mediated energy-dependent endocytosis pathway.The production of ROS and the rupture of lysosomes from Te-NDs under irradiation can promote their cytoplasmic translocation,preferably enhancing the effect of photodynamic therapy.The cytotoxicity of Te-NDs combined with photothermal and photodynamic effects increased significantly,indicating synergistic effect of PTT/PDT.Chapter 4.In vivo studies have found that Te-NDs have good tumor targeting and retention ability,and high biosafety.Te-NDs can also be induced by near-infrared light to produce heat and ROS in vivo,exhibiting photothermal and photodynamic synergistic therapy to achieve the effective tumorablation.