Dual Effect Mesoporous Silicon Oxide Drug Carrier System For Low-energy Ultrasound Antitumor Treatment

Malignant tumors are the major threats to the worldwide human life.In order to solve this problem,scientist have devoted a lot of time and effort to developing a safe and effective treatment.Chemotherapy is a traditional method of cancer treatment.In this study,we had constructed a folic-acid-tageted multifunctional mesoporous silica carrier system for low-energy ultrosound mediated chemo-sonodynamic therapy.Functional mesoporous silica was not only beneficial to the storage of PTX,but also to enhanced the cavitation effect under mild LEUS(?1.0 W·cm-2,1 MHz).Compared with the single treatment mode,the lower cell survival rate in vitro and a highly efficient tumor-growth inhibition rate in vivo by DESN under LEUS were observed.The dualmode sonodynamic therapy and chemotherapy has potential to be a safer and more effective treaments for cancer.(1)A paclitaxel(PTX)carrier system with hydrophobic internal nanovoid(DEHS)was prepared by using hollow mesoporous silica nanospheres(HMSN)with a size of 400 nm as a matrix material.The existence of hydrophobic internal nanovoid and PTX effectively improved the cavitation effect under low-energy ultrasound(LEUS,1MHz,?1.0 W·cm-2).Meanwhile,LEUS speeded up the release of PTX from DESN and increased the permeability of cell membrane in cancer cells,which greatly increased the utilization of the drug.Significant cancer cell killing effect was abserved in cancer cells treated with the DEHS together with the LEUS.Cell viability shows distinct dependency on nanoagent concentration and ultrasound intensity.In contrast,antitumor effect was not observed when LEUS applied alone.(2)A folic-acid-tageted multifunctional mesoporous silica carrier system(DESN)for low-energy ultrasound targeted chemo-sonodynamic therapy was prepared by using mesoporous silica with smaller size and easy to be phagocytic as matrix material.The existence of hydrophobic internal nanovoid and PTX effectively improved the cavitation effect under low-energy ultrasound(LEUS,1MHz,?1.0W·cm-2).Meanwhile,LEUS speeded up the release of PTX from DESN and increases the permeability of cell membrane in cancer cells,which greatly increased the utilization of the drug.The resultant DESN showed selective targeting,resulting in a strong cellular uptake of DESN for breast cancer 4T1 cells with FA receptor.Our pilot small-scale toxicity study in Kumming mice showed no obvious sign of toxic side effect.Significant cancer cell killing effect was abserved in cancer cells treated with the DESN together with the LEUS,and showed distinct dependency on nanoagent concentration and ultrasound intensity.To investigate the in vivo antitumor efficacy of the DESN by LEUS irradiation,we established a 4T1 mammary tumor model.Before in vivo administration,the DESN were confirmed to be of great biodegradability /biocompatibility.Then,the mice treated with different dose of DESN.The DESN(5 mg/kg)+LEUS group has obvious effect on tumor growth retardation(V/V0=9.38±1.35),compared with PBS(V/V0=17.12±2.75).And the tumor growth could be more significantly suppressed in the DESN(10 mg/kg)+LEUS group,the relative tumor volume reduced to 4.72±0.70.The DESN with LEUS represents excellent inhibiting effect on tumor cell in vivo.This work demonstrates that DESN mediating dual mode chemo-sonodynamic therapy can be trigged by remote control,which is of capital importance for future application in cancer therapy.