Targeted drugs could significantly reduce cytotoxic effect and increase therapeutic activity. Dihydroartemisinin (DHA) has been shown to be effective in killing cancer cells. However, it exhibits non-targeted property...Targeted drugs could significantly reduce cytotoxic effect and increase therapeutic activity. Dihydroartemisinin (DHA) has been shown to be effective in killing cancer cells. However, it exhibits non-targeted property. Holo-transferrin (TF) is a suitable drug-carrier to target cancer cells, because cancer cells need iron uptake by the TF-mediated mechanism to maintain their uncontrolled growth. Furthermore, TF receptors (TF-R) are highly expressed on cancer cell surfaces. In this paper, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the different killing effect of 4-(12-Dihydroartemisininoxy) Benzoic Acid Hydrozide-transferrin (DBAH-TF) on human breast cancer cells (MCF-7) cells and human normal breast (HNB) cells, and atomic force microscopy (AFM) was used to visually observe the targeted effect of DBAH-TF on MCF-7 cells. MTT results show that DBAH-TF is 172 times more potent than DHA in killing MCF-7 cells, while the cytotoxic effect of DBAH-TF on HNB cells is merely 1/33 to DHA. Also, the killing effect of DBAH-TF on MCF-7 cells is 286 times that on HNB cells, showing targeted effect. Moreover, there are distinct differences in ultrastructures of cellular surfaces after DBAH-TF and DHA treatment. Through AFM imaging, many characteristic holes were observed on the cancer cell surface after being effected by DBAH-TF, which differ from the holes with irregular shapes affected by DHA. These results visually show that the DBAH-TF targeted drug has more potent killing effect on MCF-7 cells compared with DHA.展开更多
During the past decade,semiconducting polymer dots(Pdots)have been prevailing in the family of fluorescent probes due to its high photon budget,excellent photo stability,and good biocompatibility.In this study,holo-Tr...During the past decade,semiconducting polymer dots(Pdots)have been prevailing in the family of fluorescent probes due to its high photon budget,excellent photo stability,and good biocompatibility.In this study,holo-Transferrin human(Tf)was utilized to covalently couple with Pdots for a highly efficient endocytosis process through transferrin receptors(TfRs)mediated internalization.As a result,the endocytosis efficiency of Tf-conjugated Pdots in HeLa cells dramatically increased as compared to that of unconjugated Pdots in the same condition.This acute increment demonstrates that holo-Transferrin molecules are of great capability for intracellular delivery of Pdots to TfRs overexpressed cells.The transportation route of Tf-conjugated Pdots is quite different from the uptake mechanism of unconjugated Pdots via nonspecific endocytic trafficking pathway.Considering the overexpression of TfRs in various cancer cells,Tf-conjugated Pdots hold potential to function as a nanocarrier for efficient drug delivery in cancer diagnostics and therapy.展开更多
The interaction between transferrin (Tf) and its antibody was investigated by atomic force microscope. Tf-antibody was immobilized on the Au-coated glass slide, and the specific combination between antibody and antige...The interaction between transferrin (Tf) and its antibody was investigated by atomic force microscope. Tf-antibody was immobilized on the Au-coated glass slide, and the specific combination between antibody and antigen was also character-ized by AFM. The results showed that holo-transferrin was jogged with anti-transferrin, and binded anti-tran- sferrin more tightly than apo-transferrin. The force- distance curves revealed that the affinity of anti-trans- ferrin and holo-transferrin was much stronger than that of apo-transferrin.展开更多
基金supported by the National Key Basic Research and Devel-opment Program of China (2010CB833603)the National Natural Science Foundation of China (30828023)
文摘Targeted drugs could significantly reduce cytotoxic effect and increase therapeutic activity. Dihydroartemisinin (DHA) has been shown to be effective in killing cancer cells. However, it exhibits non-targeted property. Holo-transferrin (TF) is a suitable drug-carrier to target cancer cells, because cancer cells need iron uptake by the TF-mediated mechanism to maintain their uncontrolled growth. Furthermore, TF receptors (TF-R) are highly expressed on cancer cell surfaces. In this paper, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the different killing effect of 4-(12-Dihydroartemisininoxy) Benzoic Acid Hydrozide-transferrin (DBAH-TF) on human breast cancer cells (MCF-7) cells and human normal breast (HNB) cells, and atomic force microscopy (AFM) was used to visually observe the targeted effect of DBAH-TF on MCF-7 cells. MTT results show that DBAH-TF is 172 times more potent than DHA in killing MCF-7 cells, while the cytotoxic effect of DBAH-TF on HNB cells is merely 1/33 to DHA. Also, the killing effect of DBAH-TF on MCF-7 cells is 286 times that on HNB cells, showing targeted effect. Moreover, there are distinct differences in ultrastructures of cellular surfaces after DBAH-TF and DHA treatment. Through AFM imaging, many characteristic holes were observed on the cancer cell surface after being effected by DBAH-TF, which differ from the holes with irregular shapes affected by DHA. These results visually show that the DBAH-TF targeted drug has more potent killing effect on MCF-7 cells compared with DHA.
基金the grants from the National Natural Science Foundation of China(Grant Nos.6133500181771930)Shenzhen Science and Technology Innovation Commission(Grant No.JCYJ20170307110157501).
文摘During the past decade,semiconducting polymer dots(Pdots)have been prevailing in the family of fluorescent probes due to its high photon budget,excellent photo stability,and good biocompatibility.In this study,holo-Transferrin human(Tf)was utilized to covalently couple with Pdots for a highly efficient endocytosis process through transferrin receptors(TfRs)mediated internalization.As a result,the endocytosis efficiency of Tf-conjugated Pdots in HeLa cells dramatically increased as compared to that of unconjugated Pdots in the same condition.This acute increment demonstrates that holo-Transferrin molecules are of great capability for intracellular delivery of Pdots to TfRs overexpressed cells.The transportation route of Tf-conjugated Pdots is quite different from the uptake mechanism of unconjugated Pdots via nonspecific endocytic trafficking pathway.Considering the overexpression of TfRs in various cancer cells,Tf-conjugated Pdots hold potential to function as a nanocarrier for efficient drug delivery in cancer diagnostics and therapy.
文摘The interaction between transferrin (Tf) and its antibody was investigated by atomic force microscope. Tf-antibody was immobilized on the Au-coated glass slide, and the specific combination between antibody and antigen was also character-ized by AFM. The results showed that holo-transferrin was jogged with anti-transferrin, and binded anti-tran- sferrin more tightly than apo-transferrin. The force- distance curves revealed that the affinity of anti-trans- ferrin and holo-transferrin was much stronger than that of apo-transferrin.
