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Single peptide ligand-functionalized uniform hollow mesoporous silica nanoparticles achieving dual-targeting drug delivery to tumor cells and angiogenic blood vessel cells.

Liu Y, Chen Q, Xu M, Guan G, Hu W, Liang Y, Zhao X, Qiao M, Chen D, Liu H - Int J Nanomedicine (2015)

Bottom Line: An in vitro pharmacodynamic study and a study of the mechanism via which the nanoparticles were endocytosed were also performed.Further, the pharmacodynamic study suggested that, compared with their unmodified counterparts, doxorubicin-loaded tHMSN had an enhanced inhibitory effect on MDA-MB-231 cells and HUVECs in vitro.Finally, a preliminary study on the mechanism by which the nanoparticles were endocytosed indicated that the clathrin-mediated endocytosis pathway has a primary role in the transport of tHMSN into the cytoplasm. tHMSN might serve as an effective active targeting nanocarrier strategy for anti-mammary cancer drug delivery.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China ; Department of Pharmacy, Bengbu Medical College, Bengbu, People's Republic of China.

ABSTRACT

Background: The purpose of this study was to construct hollow mesoporous silica nanoparticles (HMSN) decorated with tLyp-1 peptide (tHMSN) for dual-targeting drug delivery to tumor cells and angiogenic blood vessel cells.

Methods: HMSN were synthesized de novo using a novel cationic surfactant-assisted selective etching strategy and were then modified with tLyp-1. Multiple methods, including transmission electron microscopy, X-ray photoelectron spectroscopy, thermogravimetric analysis, bicinchoninic acid assay, and nitrogen adsorption and desorption isotherms, were used to characterize the tHMSN. Doxorubicin were chosen as the model cargo, and the uptake of doxorubicin-loaded tHMSN into MDA-MB-231 cells and human umbilical vein endothelial cells (HUVECs), as models of tumor cells and tumor neovascular endothelial cells, respectively, were observed and detected by confocal laser scanning microscopy and flow cytometry. An in vitro pharmacodynamic study and a study of the mechanism via which the nanoparticles were endocytosed were also performed.

Results: HMSN with a highly uniform size and well oriented mesopores were synthesized. After tHMSN were characterized, enhanced uptake of the cargo carried by tHMSN into MDA-MB-231 cells and HUVECs compared with that of their unmodified counterparts was validated by confocal laser scanning microscopy and flow cytometry at the qualitative and quantitative levels, respectively. Further, the pharmacodynamic study suggested that, compared with their unmodified counterparts, doxorubicin-loaded tHMSN had an enhanced inhibitory effect on MDA-MB-231 cells and HUVECs in vitro. Finally, a preliminary study on the mechanism by which the nanoparticles were endocytosed indicated that the clathrin-mediated endocytosis pathway has a primary role in the transport of tHMSN into the cytoplasm.

Conclusion: tHMSN might serve as an effective active targeting nanocarrier strategy for anti-mammary cancer drug delivery.

No MeSH data available.


Related in: MedlinePlus

Cellular association of doxorubicin-loaded tHMSN in the presence of different endocytosis inhibitors in MDA-MB-231 cells (A) and human umbilical vein endothelial cells (B). The geometric mean of fluorescence for cells treated with tHMSN without any inhibitors was defined as 100% (n=3).Notes: *P<0.05, **P<0.01.Abbreviations: tHMSN, tLyp-1 and polyethylene glycol co-modified hollow mesoporous silica nanoparticles; M-β-CD, methyl-β-cyclodextrin.
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f10-ijn-10-1855: Cellular association of doxorubicin-loaded tHMSN in the presence of different endocytosis inhibitors in MDA-MB-231 cells (A) and human umbilical vein endothelial cells (B). The geometric mean of fluorescence for cells treated with tHMSN without any inhibitors was defined as 100% (n=3).Notes: *P<0.05, **P<0.01.Abbreviations: tHMSN, tLyp-1 and polyethylene glycol co-modified hollow mesoporous silica nanoparticles; M-β-CD, methyl-β-cyclodextrin.

Mentions: To explore the endocytic pathway of tHMSN further, the influence of different endocytosis inhibitors (competitive and noncompetitive) on the rate of uptake of the doxorubicin-loaded nanomaterials by cells was investigated by flow cytometry. The results shown that free tLyp-1, as the competitive inhibitors, were effective in inhibiting the uptake of tHMSN into cytoplasma of MDA-MB-231 (Figure 10A, P<0.01) or HUVECs (Figure 10B, P<0.01). This finding indicates that the tLyp-1 peptide, when covalently linked to tHMSN, has an important role in the uptake of these nanoparticles. Meanwhile, investigation of the inhibitory effect of five noncompetitive endocytosis inhibitors (chlorpromazine, colchicine, genistein, wortmannin, and methyl-β-cyclodextrin) on the uptake of tHMSN into the cytoplasm of MDA-MB-231 (Figure 10A, P<0.01) and HUVECs (Figure 10B, P<0.05) showed that chlorpromazine both had the strongest inhibitory effect. These results demonstrate (or at least to some extent indicate) that clathrin-mediated endocytosis might play a primary role in transport of tHMSN into the cytoplasm.49


Single peptide ligand-functionalized uniform hollow mesoporous silica nanoparticles achieving dual-targeting drug delivery to tumor cells and angiogenic blood vessel cells.

Liu Y, Chen Q, Xu M, Guan G, Hu W, Liang Y, Zhao X, Qiao M, Chen D, Liu H - Int J Nanomedicine (2015)

Cellular association of doxorubicin-loaded tHMSN in the presence of different endocytosis inhibitors in MDA-MB-231 cells (A) and human umbilical vein endothelial cells (B). The geometric mean of fluorescence for cells treated with tHMSN without any inhibitors was defined as 100% (n=3).Notes: *P<0.05, **P<0.01.Abbreviations: tHMSN, tLyp-1 and polyethylene glycol co-modified hollow mesoporous silica nanoparticles; M-β-CD, methyl-β-cyclodextrin.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4358692&req=5

f10-ijn-10-1855: Cellular association of doxorubicin-loaded tHMSN in the presence of different endocytosis inhibitors in MDA-MB-231 cells (A) and human umbilical vein endothelial cells (B). The geometric mean of fluorescence for cells treated with tHMSN without any inhibitors was defined as 100% (n=3).Notes: *P<0.05, **P<0.01.Abbreviations: tHMSN, tLyp-1 and polyethylene glycol co-modified hollow mesoporous silica nanoparticles; M-β-CD, methyl-β-cyclodextrin.
Mentions: To explore the endocytic pathway of tHMSN further, the influence of different endocytosis inhibitors (competitive and noncompetitive) on the rate of uptake of the doxorubicin-loaded nanomaterials by cells was investigated by flow cytometry. The results shown that free tLyp-1, as the competitive inhibitors, were effective in inhibiting the uptake of tHMSN into cytoplasma of MDA-MB-231 (Figure 10A, P<0.01) or HUVECs (Figure 10B, P<0.01). This finding indicates that the tLyp-1 peptide, when covalently linked to tHMSN, has an important role in the uptake of these nanoparticles. Meanwhile, investigation of the inhibitory effect of five noncompetitive endocytosis inhibitors (chlorpromazine, colchicine, genistein, wortmannin, and methyl-β-cyclodextrin) on the uptake of tHMSN into the cytoplasm of MDA-MB-231 (Figure 10A, P<0.01) and HUVECs (Figure 10B, P<0.05) showed that chlorpromazine both had the strongest inhibitory effect. These results demonstrate (or at least to some extent indicate) that clathrin-mediated endocytosis might play a primary role in transport of tHMSN into the cytoplasm.49

Bottom Line: An in vitro pharmacodynamic study and a study of the mechanism via which the nanoparticles were endocytosed were also performed.Further, the pharmacodynamic study suggested that, compared with their unmodified counterparts, doxorubicin-loaded tHMSN had an enhanced inhibitory effect on MDA-MB-231 cells and HUVECs in vitro.Finally, a preliminary study on the mechanism by which the nanoparticles were endocytosed indicated that the clathrin-mediated endocytosis pathway has a primary role in the transport of tHMSN into the cytoplasm. tHMSN might serve as an effective active targeting nanocarrier strategy for anti-mammary cancer drug delivery.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China ; Department of Pharmacy, Bengbu Medical College, Bengbu, People's Republic of China.

ABSTRACT

Background: The purpose of this study was to construct hollow mesoporous silica nanoparticles (HMSN) decorated with tLyp-1 peptide (tHMSN) for dual-targeting drug delivery to tumor cells and angiogenic blood vessel cells.

Methods: HMSN were synthesized de novo using a novel cationic surfactant-assisted selective etching strategy and were then modified with tLyp-1. Multiple methods, including transmission electron microscopy, X-ray photoelectron spectroscopy, thermogravimetric analysis, bicinchoninic acid assay, and nitrogen adsorption and desorption isotherms, were used to characterize the tHMSN. Doxorubicin were chosen as the model cargo, and the uptake of doxorubicin-loaded tHMSN into MDA-MB-231 cells and human umbilical vein endothelial cells (HUVECs), as models of tumor cells and tumor neovascular endothelial cells, respectively, were observed and detected by confocal laser scanning microscopy and flow cytometry. An in vitro pharmacodynamic study and a study of the mechanism via which the nanoparticles were endocytosed were also performed.

Results: HMSN with a highly uniform size and well oriented mesopores were synthesized. After tHMSN were characterized, enhanced uptake of the cargo carried by tHMSN into MDA-MB-231 cells and HUVECs compared with that of their unmodified counterparts was validated by confocal laser scanning microscopy and flow cytometry at the qualitative and quantitative levels, respectively. Further, the pharmacodynamic study suggested that, compared with their unmodified counterparts, doxorubicin-loaded tHMSN had an enhanced inhibitory effect on MDA-MB-231 cells and HUVECs in vitro. Finally, a preliminary study on the mechanism by which the nanoparticles were endocytosed indicated that the clathrin-mediated endocytosis pathway has a primary role in the transport of tHMSN into the cytoplasm.

Conclusion: tHMSN might serve as an effective active targeting nanocarrier strategy for anti-mammary cancer drug delivery.

No MeSH data available.


Related in: MedlinePlus