Synthesis Of Precious Metal Nanoparticles Mediated Photothermal Therapy For Bladder Cancer

Bladder cancer is one of the most common malignancies of urinary system.Worldwide,the incidence of bladder cancer ranks 9th among malignant tumors,7th among males（9.5 per 100,000）and 10th among females（2.410 per 100,000）.The mortality rate was the 13th highest among malignant tumors,with a mortality rate of3.2 per 100,000 males and 0.9 per 100,000 females.At present,surgery,radiotherapy and chemotherapy are the conventional methods for the treatment of bladder cancer.However,due to the high recurrence rate after surgery,and the toxic side effects of radiotherapy and chemotherapy,the cancer cure rate is maintained at a very low level.Photothermal therapy（PTT）,as a new non-invasive tumor therapy technology,has become a hot spot in the field of tumor therapy due to its advantages of local,high efficiency and low side effects.In PTT,photothermal agents convert light energy into heat energy under near-infrared laser irradiation to induce apoptosis of cancer cells.Among them,photothermal agent is the core of PTT.Through the modification of photothermal nanomaterials,the functions of photothermal nanomaterials are increasing.Among them,inorganic nano photothermal materials have attracted much attention because of their advantages such as easy preparation,easy modification,high efficiency photothermal conversion and low price.However,the photothermal conversion efficiency,biocompatibility,safety and biodegradability of photothermal agents are still important factors that need to be solved urgently.Based on this,this paper designed and constructed a new type of nanoparticles based on precious metals.At the same time,combined with radiation therapy（RT）and chemodynamic therapy（CDT）,the effective synergistic treatment of bladder cancer was obtained.At the same time,the potential value of precious metals nanoparticles in biomedicine was also discussed.This paper mainly includes four parts:（1）In the first part,nanorods Pd Te（Pd Te NR）was synthesized by one-pot in-situ reduction method.Through the study of physical and chemical properties and structure,Pd Te not only has the characteristics of high photothermal conversion efficiency and good photostability,but also has CAT-like properties that can decompose H₂O₂ into O₂,so as to overcome anoxia and improve the effect of thermal-radiotherapy.Since Pd and Te are typical High-Z elements that can enhance the dose deposition of X-ray,Pd Te nanoparticles show significant radiosensitization ability in tumor cells.Subsequently,using MBT-2 tumor cells as models,studies have shown that Pd Te nanoparticles enhance the therapeutic effect of thermal-radiotherapy and have good biological safety.（2）In the second part,a nanotherapeutic platform of Pd Te NR nanoparticles in combination with thermoradiotherapy was constructed using MBT-2 tumor-bearing mice as a model.The results showed that the Pd Te NR-mediated thermoradiotherapy successfully induced tumor ablation.With this,the tumor site hypoxia was significantly improved in mice after photothermal treatment,and the therapeutic effect of radiotherapy was greatly improved.The blood biochemical indices of the animals showed that Pd Te NR has good stability and biosafety in vivo,thus Pd Te NR is a promising multifunctional nanoparticle with great potential for enhanced radiation therapy.（3）In the third part,ultra-small copper-palladium nanoparticles（CP NPs）with high catalytic activity were prepared and used for synergistic CDT and PTT for tumor therapy.After the CP NPs accumulated in the tumor region and entered the tumor cells,the copper ions(Cu²⁺)reacted with intracellular GSH to reduce its level.Next,the formed cuprous ions（Cu⁺）reacted with the overexpressed H₂O₂ at the tumor site to generate a large amount of toxic hydroxyl radicals（?OH）,which induced cell death.In addition,under 808 nm laser irradiation,CP NPs exhibited significant photothermal conversion rate and specific ablation of tumor tissues,which further enhanced the therapeutic effect of CDT.In cellular experiments,CP NPs significantly inhibited the growth of bladder cancer cells（MB-49）in synergistic CDT and PTT combination therapy,which fully confirmed the efficient chemodynamic-photothermal synergistic therapeutic effect of CP NPs.（4）In the fourth part,MB-49 mouse animals were used as a model to continue the in-depth investigation of the in vivo antitumor therapeutic effect of CP NPs.The results showed that CP NPs-mediated CDT/PTT successfully induced tumor death.At the same time,the blood biochemical parameters of the animals showed good stability and biosafety in vivo,which provides a new idea for the precision treatment of tumors.In summary,based on the interdisciplinary research of medicine,inorganic chemistry and biology,this paper conducted a more in-depth study on the photothermal treatment of bladder cancer by precious metal nanoparticles,and provided new scientific research ideas and theoretical basis for the treatment of bladder cancer by nano drugs.