The Functional Design And Anticancer Activity Of Targeted Boron Nitride Nanotubes-based Drug Delivery System

Boron nitride nanotubes(BNNTs)have attracted considerable attention in the biomedical field because of their unique physicochemical properties and excellent biocompatibilities.However,the utilization of BNNTs in this field is still in the preliminary stage.So far,only a few studies on the utilization of BNNTs as drug carrier have been reported,and the relevant antitumor mechanism has not been investigated.In this thesis,BNNTs were modified by folate(FA),which were then used to carry Auristatin PE(PE),and the cell uptake,anti-tumor behavior and mechanism were systematically studied.In addition,the cytotoxicity of boron carbonitride nanotubes(BCNNTs),an analogue of BNNTs,was discussed,laying a theoretical foundation for the study of BCNNTs in the biomedical field.(1)BNNTs were synthesized using an improved solid-state reaction developed in our group.These prepared BNNTs have an average diameter of about 90 nm,good thermal stability and photoluminescence properties.The cytotoxicities of BNNTs-OH on five cell lines including two normal cells(L02 cells,HEK 293ft cells)and three tumor cells(Hep G2 cells,MDA-MB-231 cells and PC-3 cells)were studied.The results showed that BNNTs-OH is non-toxic or low-toxic to normal cells,but it has toxic to tumor cells.(2)BCNNTs were prepared using amorphous boron powder and natural latex as raw materials and FeCl3·6H2O as catalyst.The cytotoxicities of BCNNTs-OH on five cell models including two normal cells(L02 cells,HEK 293ft cells)and three tumor cells(Hep G2 cells,MDA-MB-231 cells and PC-3 cells)were studied.The results indicated that BCNNTs-OH is non-toxic to normal cells(L02 cells)and low toxic to HEK 293ft cells,and BCNNTs-OH has better safety than BNNTs-OH.BCNNTs-OH is toxic to the tumor cells,and the toxicity order is MDA-MB-231>Hep G2>PC-3.These results indicated that BCNNTs can be applied as a potential nanomaterial with anti-tumor activity and good biosafety.(3)The drug delivery system against liver cancer cells(Hep G2 cells)based on BNNTs-OH and PE was constructed.The cellular uptake and antitumor effects of BNNTs@PE against Hep G2 cells were studied.The results showed that PE could be delivered into cells by BNNTs@PE through an endocytosis pathway.BNNTs@PE demonstrates an enhanced antitumor activity against Hep G2 cells in comparison with free PE,which is manifested as decreased cell activity and induced apoptosis.(4)A novel targeted drug delivery system against liver cancer cells based on FA conjugated BNNTs(BNNTs-FA)and PE was constructed.The carrier,BNNTs-FA,shows better stability and biosafety than BNNTs-OH.The uptake and antitumor effects of BNNTs-FA@PE against Hep G2 cells and the related mechanisms were studied.The results showed that PE can be delivered into cells by BNNTs@PE through an endocytosis pathway assisted with FA receptor-mediated endocytosis pathway,enhancing the internalization and cytotoxicity of PE.BNNTs-FA@PE exhibits stronger cytotoxicity to Hep G2 cells than free PE and BNNTs@PE.BNNTs-FA@PE kills tumor cells by reducing cells viability,inhibiting cells proliferation,and inducing cells apoptosis via a mitochondria-mediated apoptosis pathway.