Application Of Triple Targeting Organic Nanoparticles In Phototherapy Of Tumor

In recent years,the incidence of tumor is increasing,attracting more and more researchers' attention.Traditional tumor drugs lead to tissue resistance and serious side effects due to their lack of tissue targeting.Phototherapy is one of the most promising tumor treatment tools,due to the advantages of less invasive,easy to operate and low toxicity.However,photodynamics therapy(PDT)process is limited by reactive oxygen species production,and photothermal therapy(PTT)produces tissue heat tolerance after initial treatment.The combination of PDT and PTT is a breakthrough strategy.Because PTT could heighten the oxygen concentration by increasing the flow rate of blood to strengthen the PDT effect,thus promoting the elimination of heat-resistant tumor in PTT reversely.Synergistic PDT/PTT therapy can overcome their shortcomings and enhance the effect of collaborative therapy.The construction of synergistic phototherapy platform has a good application prospect for tumor therapy.Nanotechnology has been serving as a simple and nonchemical approach to deliver drugs to cells of interest or specific organelles,such as mitochondria and nucleus without changing the nature of the drug itself.In this paper,the fluorescence molecule BTPB-Py with A-D-A structure was prepared by simple synthesis reaction,and the organic nanoparticle FA-BTPB-Py for synergistic phototherapy was prepared based on the BTPB-Py.The introduction of pyridine group enables the mitochondrial targeting of BTPB-Py molecule,and folic acid functionalization on the surface of the nanoparticles can cause specific interactions with tumor cells overexpressed by folic acid receptor,and subsequently accumulate in the mitochondria.FA-BTPB-Py nanoparticles exhibit high reactive oxygen generation and good photothermal conversion ability in complex biological systems.Using confocal laser microscopy to study the imaging ability of nanoparticles in He La cells,we are pleasantly surprised to find that nanoparticles could enter not only mitochondria but also the nucleus.Therefore,FA-BTPB-Py nanoparticles can not only generate reactive oxygen species required by PDT process in mitochondria,but also kill tumor cells in heat-sensitive nucleus through heat generated during PTT process,enhancing the therapeutic effects of PDT and PTT.It is noteworthy that FA-BTPB-Py nanoparticles had good PDT/PTT synergistic phototherapy effect in vivo experiments,and tumor was completely eliminated after treatment.Hence,this paper demonstrates a method for preparing organic nanoparticles that target tumor cells,mitochondria and nucleus,opening up new opportunities for triple-targeted drug delivery and therapy.