Multifunctional Polyaniline-based Hydrogels With Deep Tissue Penetration Capability For Cancer Therapy

In recent years,drug delivery systems based on nanotechnology have received extensive attention from researchers.However,during the treatment process,the physiological barrier of tumor tissue often hinders the penetration of foreign nanoparticles into the tumor,making it difficult to deliver anti-cancer drugs,and single-drug treatment is likely to cause tumor cells to become resistant,which is extremely affect the effect of tumor treatment.Therefore,it is of great significance to design a drug delivery system that can not only increase the depth of tumor treatment,but also achieve synergistic treatment.This thesis constructs a new type of nano drug delivery system,adopts multiple strategies to achieve deep penetration of drugs in the tumor area,and uses the excellent photoacoustic imaging performance and photothermal conversion properties of polyaniline to achieve real-time tracking of the drug penetration process,while performing photothermal-chemotherapy synergistic treatment,which ultimately improves the effect of tumor treatment.The specific content includes the following three parts:(1)Preparation of multifunctional polyaniline-polyacrylic acid composite nanoparticles.Firstly,polyaniline nanoparticles were prepared by hydrothermal method,and then multifunctional polyaniline-polyacrylic acid composite nanoparticles were prepared by reflux precipitation polymerization.In this process,the influence of different monomer ratios and reaction time on the synthesis of polyaniline-polyacrylic acid composite nanoparticles was explored.The results show that the polyaniline-polyacrylic acid composite nanoparticles are uniform in size,with a particle size distribution of about 245 nm,and the surface of the material is negatively charged.It can load the positively charged anticancer drug doxorubicin(DOX)through electrostatic adsorption.In addition,the drug-loaded nanoparticles have excellent near-infrared photothermal heating performance and photoacoustic imaging properties,which lay the foundation for the subsequent construction of a composite hydrogel drug delivery system to realize image-guided photothermal-chemotherapy synergistic treatment.(2)Construction of a multifunctional composite hydrogel drug delivery system and its application in tumor treatment.The injectable hydrogel is prepared by the electrostatic attraction interaction of polyelectrolyte,and the drug-loaded nanoparticles and collagenase are combined to construct a multifunctional composite hydrogel drug delivery system.The drug delivery system can realize the gradual release of collagenase and drug loaded polyaniline nanoparticles to achieve deep treatment.In vitro cell experiments show that the composite hydrogel drug delivery system has good biocompatibility and can effectively inhibit the proliferation of tumor cells.The inhibition rates on tumor cells at 24 h and 48 h are 70.3% and 77.5%,respectively.In vivo anti-tumor experiments show that the composite hydrogel drug delivery system has a significant inhibitory effect on tumor volume in mice.(3)The construction of stimulus-responsive nanohydrogel with adjustable size and its application in tumor treatment.The multifunctional tetrapolyaniline-nanohydrogel is prepared by reflux precipitation polymerization method and chemical coupling,and the nanohydrogel drug delivery system is constructed by using electrostatic adsorption to load DOX.The drug delivery system has good photothermal conversion performance and photoacoustic imaging properties,and the temperature-controlled size of the nanohydrogel is adjustable,which also provides a basis for subsequent deep therapy.Tumor suppression experiments in mice show that the nanohydrogel drug delivery system has a good tumor suppression effect,and is expected to become a reliable platform for deep therapy and synergistic treatment.