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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

X-ray photoelectron spectra (A) and thermogravimetric analysis curves (B) for HMSN, tHMSN, or pHMSN.Abbreviations: HMSN, hollow mesoporous silica nanoparticles; tHMSN, tLyp-1 and polyethylene glycol co-modified HMSN; pHMSN, polyethylene glycol-modified HMSN.
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f4-ijn-10-1855: X-ray photoelectron spectra (A) and thermogravimetric analysis curves (B) for HMSN, tHMSN, or pHMSN.Abbreviations: HMSN, hollow mesoporous silica nanoparticles; tHMSN, tLyp-1 and polyethylene glycol co-modified HMSN; pHMSN, polyethylene glycol-modified HMSN.

Mentions: Zeta potential, bicinchoninic acid, X-ray photoelectron spectroscopy, and thermogravimetric analysis assays were carried out to confirm surface modification of the nanoparticles. The particle size of tHMSN and pHMSN showed minor amplification when compared with HMSN, but the zeta potential showed a more marked change (Figure 3B). This change could be attributed to the different chemical groups on the surfaces of the nanoparticles, including a silicon hydroxyl group (Si-OH) on HMSN, a primary amino group (NH2) on HMSN-NH2, and an alkyl hydroxyl group (CH2-OH) originating from PEG (or β-mercaptoethanol) on pHMSN and tHMSN. Further, bicinchoninic acid assay identified peptides on the surfaces of tHMSN but not on pHMSN or HMSN. X-ray photoelectron spectroscopy, a surface chemical analysis technique, was performed. Comparing the X-ray photoelectron spectrum (Figure 4A) of tHMSN with that of HMSN, the peaks seen at 400.2 eV and 286.2 eV indicate that there were additional N and C elements on the surface of tHMSN, which were resourced from tLyp-1 peptide and PEG, respectively. But such elements were not found in HMSN.


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)

X-ray photoelectron spectra (A) and thermogravimetric analysis curves (B) for HMSN, tHMSN, or pHMSN.Abbreviations: HMSN, hollow mesoporous silica nanoparticles; tHMSN, tLyp-1 and polyethylene glycol co-modified HMSN; pHMSN, polyethylene glycol-modified HMSN.
© Copyright Policy
Related In: Results  -  Collection

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

f4-ijn-10-1855: X-ray photoelectron spectra (A) and thermogravimetric analysis curves (B) for HMSN, tHMSN, or pHMSN.Abbreviations: HMSN, hollow mesoporous silica nanoparticles; tHMSN, tLyp-1 and polyethylene glycol co-modified HMSN; pHMSN, polyethylene glycol-modified HMSN.
Mentions: Zeta potential, bicinchoninic acid, X-ray photoelectron spectroscopy, and thermogravimetric analysis assays were carried out to confirm surface modification of the nanoparticles. The particle size of tHMSN and pHMSN showed minor amplification when compared with HMSN, but the zeta potential showed a more marked change (Figure 3B). This change could be attributed to the different chemical groups on the surfaces of the nanoparticles, including a silicon hydroxyl group (Si-OH) on HMSN, a primary amino group (NH2) on HMSN-NH2, and an alkyl hydroxyl group (CH2-OH) originating from PEG (or β-mercaptoethanol) on pHMSN and tHMSN. Further, bicinchoninic acid assay identified peptides on the surfaces of tHMSN but not on pHMSN or HMSN. X-ray photoelectron spectroscopy, a surface chemical analysis technique, was performed. Comparing the X-ray photoelectron spectrum (Figure 4A) of tHMSN with that of HMSN, the peaks seen at 400.2 eV and 286.2 eV indicate that there were additional N and C elements on the surface of tHMSN, which were resourced from tLyp-1 peptide and PEG, respectively. But such elements were not found in HMSN.

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