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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 uptake after 0.5–2 hours of culture with HMSN, pHMSN, or tHMSN loaded with the same amount of doxorubicin in MDA-MB-231 cells (A, B) or human umbilical vein endothelial cells (C, D) and then detection of mean fluorescent intensity by flow cytometry. The geometric mean of fluorescence for cells treated with tHMSN after 2 hours was defined as 100% (n=3).Notes: *P<0.05, **P<0.01.Abbreviations: HMSN, hollow mesoporous silica nanoparticles; tHMSN, tLyp-1 and polyethylene glycol co-modified HMSN; NS, not statistically significant; pHMSN, polyethylene glycol-modified HMSN.
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f7-ijn-10-1855: Cellular uptake after 0.5–2 hours of culture with HMSN, pHMSN, or tHMSN loaded with the same amount of doxorubicin in MDA-MB-231 cells (A, B) or human umbilical vein endothelial cells (C, D) and then detection of mean fluorescent intensity by flow cytometry. The geometric mean of fluorescence for cells treated with tHMSN after 2 hours was defined as 100% (n=3).Notes: *P<0.05, **P<0.01.Abbreviations: HMSN, hollow mesoporous silica nanoparticles; tHMSN, tLyp-1 and polyethylene glycol co-modified HMSN; NS, not statistically significant; pHMSN, polyethylene glycol-modified HMSN.

Mentions: As expected, the flow cytometry assay demonstrated that tHMSN had the highest cellular uptake efficiency of the three types of nanoparticles when loaded with the same amount of doxorubicin (6 μg/mL), although the endocytosis of tHMSN into MDA-MB-231 cells (Figure 7A and B, P<0.01) or HUVECs (Figure 7C and D, P<0.01) was slightly higher than that of HMSN, but was significantly higher than that of their tLyp-1 unmodified counterparts (pHMSN). The lower uptake efficiency of pHMSN compared with that of HMSN can be explained by the sterically hindered effects of PEG chains grafted onto the surface of nanoparticles. However, compared with HMSN and pHMSN, tHMSN, which was tLyp-1 and PEG co-modified HMSN, exhibited higher uptake efficiency into the cytoplasm of tumor cells or angiogenic blood vessels cells and this might ascribed to the specific recognition between tLyp-1 peptide and the overexpressed receptor proteins of NRP on the cell membrane of the target cells. Confocal laser scanning microscopy was then performed to further visualize the behavior of the nanoparticles in cells. After 30 minutes of incubating the cells with nanoparticles loaded with the same amount of doxorubicin (6 μg/mL), no significant difference of the red fluorescence intensity was detected within each group. However, with extension of the incubation time to 2 hours, there was an increasingly discrepancy between the tHMSN group and the pHMSN group (Figure 8A and B).


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 uptake after 0.5–2 hours of culture with HMSN, pHMSN, or tHMSN loaded with the same amount of doxorubicin in MDA-MB-231 cells (A, B) or human umbilical vein endothelial cells (C, D) and then detection of mean fluorescent intensity by flow cytometry. The geometric mean of fluorescence for cells treated with tHMSN after 2 hours was defined as 100% (n=3).Notes: *P<0.05, **P<0.01.Abbreviations: HMSN, hollow mesoporous silica nanoparticles; tHMSN, tLyp-1 and polyethylene glycol co-modified HMSN; NS, not statistically significant; pHMSN, polyethylene glycol-modified HMSN.
© Copyright Policy
Related In: Results  -  Collection

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

f7-ijn-10-1855: Cellular uptake after 0.5–2 hours of culture with HMSN, pHMSN, or tHMSN loaded with the same amount of doxorubicin in MDA-MB-231 cells (A, B) or human umbilical vein endothelial cells (C, D) and then detection of mean fluorescent intensity by flow cytometry. The geometric mean of fluorescence for cells treated with tHMSN after 2 hours was defined as 100% (n=3).Notes: *P<0.05, **P<0.01.Abbreviations: HMSN, hollow mesoporous silica nanoparticles; tHMSN, tLyp-1 and polyethylene glycol co-modified HMSN; NS, not statistically significant; pHMSN, polyethylene glycol-modified HMSN.
Mentions: As expected, the flow cytometry assay demonstrated that tHMSN had the highest cellular uptake efficiency of the three types of nanoparticles when loaded with the same amount of doxorubicin (6 μg/mL), although the endocytosis of tHMSN into MDA-MB-231 cells (Figure 7A and B, P<0.01) or HUVECs (Figure 7C and D, P<0.01) was slightly higher than that of HMSN, but was significantly higher than that of their tLyp-1 unmodified counterparts (pHMSN). The lower uptake efficiency of pHMSN compared with that of HMSN can be explained by the sterically hindered effects of PEG chains grafted onto the surface of nanoparticles. However, compared with HMSN and pHMSN, tHMSN, which was tLyp-1 and PEG co-modified HMSN, exhibited higher uptake efficiency into the cytoplasm of tumor cells or angiogenic blood vessels cells and this might ascribed to the specific recognition between tLyp-1 peptide and the overexpressed receptor proteins of NRP on the cell membrane of the target cells. Confocal laser scanning microscopy was then performed to further visualize the behavior of the nanoparticles in cells. After 30 minutes of incubating the cells with nanoparticles loaded with the same amount of doxorubicin (6 μg/mL), no significant difference of the red fluorescence intensity was detected within each group. However, with extension of the incubation time to 2 hours, there was an increasingly discrepancy between the tHMSN group and the pHMSN group (Figure 8A and B).

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