Design Of Polypyrrole-based Drug Delivery System And Its Application In Tumor Synergy Therapy

Tumor is a disease that seriously endangers human health.Traditional treatment methods such as surgery,chemotherapy and radiotherapy have limitations and side effects such as high trauma and easy to cause damage to normal tissues,so the development of new and efficient treatment methods is an important issue in the field of tumor treatment at present.Photothermal therapy is a new therapeutic method that uses a light source to stimulate photothermal materials to generate heat,thus killing tumor cells.Photothermal therapy has the advantages of non-invasive,good selectivity and controllability,which can achieve precise positioning and local heating of the tumor and avoid damage to normal tissues.Photothermal therapy can also be synergized with other therapeutic methods,such as chemotherapy,radiotherapy,immunotherapy,etc.to achieve multiple treatments for tumors and thus improve the therapeutic effect.Therefore,photothermal therapy shows a broad application prospect in tumor treatment.Polypyrrole has high conversion ability and strong absorption peaks in the near-infrared region.At the same time,polypyrrole also has good biocompatibility and drug loading ability,so it is an ideal photothermal absorber and drug-carrying agent,and has good application prospects in the field of photothermal tumor therapy research.In this paper,two nano drug-carrying systems,PPy-Ce6 and PPy-DOX nanoparticles,were designed using polypyrrole as a nanocarrier to realize photothermal/photodynamic synergistic therapy and photothermal/chemotherapy synergistic therapy,respectively.The specific work is as follows;(1)PPy-Ce6 nanoparticles were prepared by an improved chemical oxidative polymerization method,which showed a spherical structure with a particle size of around 75nm and a uniform distribution.The PPy-Ce6 nanoparticles were successfully loaded with the photosensitizer Ce6 with an approximate loading rate of 0.14%,as calculated from the absorption spectra.The nanoparticles have good stability and can generate heat efficiently under 808nm laser illumination.The solution temperature rises by 18.6℃ when the nanoparticle concentration is 1 mg/mL and the irradiated laser power is 240mW/cm2;under 66nm laser irradiation,the single-line oxygen can be generated rapidly.PPy-Ce6 nanoparticles were applied to HeLa cells,and the results showed that the nanoparticles were biocompatible,and the mortality rate of the cells reached 60%under 808nm and 660nm laser irradiation with photothermal/photodynamic synergistic effect.(2)The design of PPy-DOX nanoparticles was divided into two parts,firstly,the PLL modified PPy nanoparticles were synthesized,and then the chemotherapeutic drug DOX was loaded using glutaraldehyde as a crosslinking agent.The aqueous-phase PPy-DOX nanoparticles with a particle size of about 200nm showed a spherical shape,and their absorption spectra had characteristic peaks of both PPy and DOX,with good photothermal properties.Under acidic conditions,the Schiff base bond is prone to fracture to release DOX,and dialysis experiments showed that the DOX release from the nanoparticles had a pH-responsive property,and when placed in a pH=5 buffer solution,about 61%of DOX was released in 6 hours,and the cumulative release rate reached 73%after 24 hours.When the laser light was increased,the DOX release rate was accelerated,and the cumulative release rate reached 90%after 24 hours.Confocal imaging experiments revealed that PPy-DOX nanoparticles could be effectively phagocytosed by Hela cells,and the cell death rate of 80%was achieved when PPy-DOX nanoparticles were applied to HeLa cells,which was superior to the single photothermal treatment of PPy and the chemotherapy of DOX to realize the efficient synergistic effect of photothermal/chemotherapy.Efficient synergistic treatment of photothermal/chemotherapy.