High Efficient Preparation,Size Control And Biomedical Applications Of Polypyrrole/ZIF-8 Nanoscale Hybrids

ZIF-8(Zeolitic Imidazole Frameworks-8)is a kind of crystalline and porous materials formed by the coordination reaction of zinc ions with 2-methylimidazole.It is an ideal carrier for drug delivery because of its high porosity,large specific surface,easy surface modification,good biocompatibility and sensitivity for acid environment.However,such as membrane devices and drug carriers have specific requirements for the particle size of nanoparticles,so it is important to control the size of ZIF-8to inprove its applications.Tumor is a disease which is harmful to human health.The traditional methods of surgery,chemotherapy and radiotherapy have serious side effects and it's easy to recur.And photothermal therapy is non-invasive,controllable,and less side effects of targeted therapy that photothermal agents convert light energy into heat to achieve the ablation of tumor under the irradiation of near-infrared light,which shows great potential applications in the treatment of tumors and other diseases.However,most of the photothermal agents are hydrophobic,which seriously limits their application in hydrophilic physiological environment.The combination of photothermal agents and ZIF-8 nanoparticles can solve this problem.In view of the above problems,we succeed in synthesizing ZIF-8 with various sizes of 52-362 nm by the the pre-balance of pyrrole.Pyrrole can reduce the nucleation rate of ZIF-8 because of its weak coordination reaction with zinc ion,so the size of ZIF-8 increases with the amount of pyrrole.The as-synthesized ZIF-8 nanoparticles have uniform size,perfect crystallization and good thermal stability.After pyrrole was introduced into the reaction system,PPy@ZIF-8nanoparticles were synthesized by in situ polymerization of pyrrole stabilized by hydroxypropyl cellulose with good biocompatibility and water solubility and initiated by Fe Cl₃ for photothermal treatment and photoacoustic imaging of tumors.The particle sizes of PPy@ZIF-8nanoparticles were 94 nm and its hydrodynamic particle size is 257 nm,respectively.The synthesized nanoparticles had strong photoacoustic signal and its photothermal conversion efficiency is 35.5%.We explored the biological application of PPy@ZIF-8 nanoparticles at cell level and animal level.It shows a good prospect in biological application in the treatment of tumor and other diseases.Only in the synergy of near infrared light and nanoparticles,can it kill tumor cells(A549 and 4T1cells)and tumor tissues,but the cell viability of A549,4T1 and HUVEC cells can keeps at 90%incubated with PPy@ZIF-8 nanoparticles of 500?g ml^-1 for24 hours without light.Pharmacokinetics shows that the half-life of PPy@ZIF-8 in SD rats was 1.48 h,which provided the possibility for its enrichment in tumor.On this basis,we used BALB/C nude mice for animal experiments,and 4T1 cells for tumor modeling.Photoacoustic imaging shows that PPy@ZIF-8 nanoparticles could be enriched in tumor within 5 h,and remained in tumor for a long time.In vivo photothermal experiments shows that PPy@ZIF-8 nanoparticles can effectively inhibit the growth of tumor tissue under near-infrared light irradiation,and will not cause significant damage to normal tissue.PPy@ZIF-8 nanoparticles shows good biocompatibility and photothermal therapy effect that in the synergy of near infrared light and nanoparticles,the cancer was inhabited without damage to healthy tissue.