Folic Acid Functionalized PH-sensitive Photothermal Therapy Traceable Hollow Mesoporous Silica Nanoparticles As A Targeted Drug Delivery System To Improve The Antitumour Effect Of Doxorubicin

Objective In this paper,we prepared doxorubicin-loaded folic acid functionalized p H-sensitive photothermal therapy traceable hollow mesoporous silica nanoparticles(DOX-HPCF)as a drug delivery system for liver cancer treatment to study the antitumor effect of this system.Methods Hollow mesoporous silica nanoparticles(HMSN)were prepared by a hard template method.Doxorubicin(DOX)was adsorbed into the mesoporous structure of HMSN by adsorption to obtain DOX-HMSN.Dopamine formed a PDA adhesive layer on the surface of DOX-HMSN through self-polymerization,forming DOX-HMSN-PDA(DOX-HP).There were a large number of amino groups on the surface of carbon quantum dots(CQDs),which could be bonded to PDA to form DOX-HMSN-PDA-CQDs(DOX-HPC).Folic acid(FA)and DOX-HPC were connected through amide bond to finally prepare a drug-loading system(DOX-HPCF).The drug carrier and drug delivery system were characterized and tested by transmission electron microscopy(TEM),fourier transform infrared spectroscopy(FT-IR),thermogravimetry(TGA)and in vitro release experiments.The MTT experiment investigated the safety of HPCF,and the cell uptake experiment examined the absorption of HPCF by SMMC-7721.Apoptosis experiments evaluated the effect of DOX-HPCF assisted near-infrared(NIR)light irradiation on the apoptosis of SMMC-7721 cells.The inhibitory effect of DOX-HPCF on subcutaneously transplanted tumors of H22 cells was studied in tumor-bearing mice,and the tumor targeting of DOX-HPCF was evaluated by in vivo biodistribution study.Results According to TEM characterization,HMSN was monodisperse spherical nanoparticles with hollow structure.FT-IR and TGA results showed that HPCF was successfully prepared.In vitro drug release experiments showed that HPCF exhibited p H-sensitive release.MTT experiments showed that HPCF had good biological safety.Cell uptake experiments showed that the ability of SMMC-7721 cells to uptake HPCF was superior to HPC.In addition,DOX-HPCF significantly inhibited the proliferation of SMMC-7721 cells,while the near-infrared(NIR)irradiation group showed a more significant inhibitory effect.In vivo anti-tumor experiments showed that DOX-HPCF assisted photothermal therapy could significantly inhibit tumor growth,and in vivo biodistribution study showed that HPCF had significant targeting.Conclusions In this study,we successfully prepared DOX-HPCF as a drug carrier for the treatment of liver cancer.HPCF could effectively transfer DOX to hepatoma cells.It could make the drug accumulate in the tumor tissue and promoted the apoptosis under the near-infrared(NIR)light irradiation.Therefore,HPCF was a promising photothermal therapy carrier for the treatment of liver cancer.