A Novel Mesoporous Titanium Dioxide Nanosystem Coated With Hyaluroic Acid And Polydopamine Shell For Multifunctional Combination Therapy Of Tumors

Traditional methods of tumor treatment are difficult to obtain the ideal effect.With the development of tumor treatment to non-toxic and non-invasive,various new methods have emerged.Compared with monotherapy,nano-systems that integrate multiple therapeutic functions are expected to achieve superior anti-tumor effects.In this study,a new multifunctional nano-system(MTN-DTX@PDA-HA)combining sonodynamic therapy(SDT),photothermal therapy(PTT)and chemotherapy was prepared.This study conducted a preliminary evaluation of the characterizations,anti-tumor effect of MTN-DTX@PDA-HA in vitro and in vivo.The first part was the preparation and characterization of MTN-DTX@PDA-HA.Objective: To prepare and characterize MTN-DTX@PDA-HA.Methods: MTN was prepared by the thermal solvent method.After the MTN was loaded with DTX,the polydopamine and hyaluronic acid shell were modified by a one-pot synthesis method,and then performed a series of characterizations on the nanoparticles Results: MTN-DTX@PDA-HA nanoparticles were successfully prepared.The nanoparticles had a uniform particle size and a fusiform shape.The specific surface area and pore size distribution of the MTN were 134.09 m2/g and 12.17 nm,respectively.The drug loading capacity and encapsulation efficiency of MTN-DTX@PDA-HA were 9.29±0.24% and 88.93±2.34%,respectively.The nanoparticles have the pH-responsive characteristics,good photothermal and sonodynamic properties.The second part was the in vitro anti-tumor study of MTN-DTX@PDA-HA.Objective: To investigate the intracellular uptake,sonodynamic properties and cell-killing ability of MTN-DTX@PDA-HA.Methods: The intracellular uptake of MTN-DTX@PDA-HA was investigated with the coumarin-6,and the reactive oxygen species(ROS)produced by the nanoparticles in cells was detected by DCFH-DAD probe.The cell-killing ability of the MTN-DTX@PDA-HA was evaluated by MTT method.Results: The HA on the surface of MTN-DTX@PDA-HA increased the uptake of nanoparticles by 4T1 cells.The sonodynamic properties did not change after MTN modified with the PDA-HA shell.The combined effects of chemotherapy,PTT and SDT can be achieved by MTN-DTX@PDA-HA under the near infrared laser and ultrasonic irradiation.The third part was the anti-tumor research of MTN-DTX@PDA-HA in vivo.Objective: To investigate the photothermal and anti-tumor effect of MTN-DTX@PDA-HA in vivo.Methods: Infrared thermal imager was used to examine the photothermal effect of the nanoparticles in vivo.The anti-tumor effect of MTN-DTX@PDA-HA was studied with 4T1 tumor-bearing mice,and the tumor tissue was further analyzed by H&E staining.Results: MTN-DTX@PDA-HA has a good photothermal effect in vivo.MTN-DTX@PDA-HA-mediated combination of chemotherapy,PTT and SDT can effectively inhibit tumor growth.