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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

Dynamic light scattering size (A) of HMSN and zeta potential (B) of tHMSN, pHMSN, HMSN-NH2, and HMSN (n=3).Abbreviations: HMSN, hollow mesoporous silica nanoparticles; tHMSN, tLyp-1 and polyethylene glycol co-modified HMSN; pHMSN, polyethylene glycol-modified HMSN.
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f3-ijn-10-1855: Dynamic light scattering size (A) of HMSN and zeta potential (B) of tHMSN, pHMSN, HMSN-NH2, and HMSN (n=3).Abbreviations: HMSN, hollow mesoporous silica nanoparticles; tHMSN, tLyp-1 and polyethylene glycol co-modified HMSN; pHMSN, polyethylene glycol-modified HMSN.

Mentions: Uniform and monodispersed SSN and HMSN were prepared following the method proposed by Fang et al37,38 with minor modifications. Transmission electron micrographs of the particles showed clearly that both SSN (Figure 2A) and HMSN (Figure 2B) had a spherical morphology and uniform particle size. The mean size of HMSN according to dynamic light scattering was 258.1±9.4 nm (n=3, Figure 3A), which was larger than the value obtained on transmission electron micrographs due to the presence of hydrated layers around the surfaces of the particles. Nitrogen adsorption– desorption isotherm measurements indicated that the HMSN had a relatively high specific surface area of 547.79 m2/g (Figure 2C) and a well-defined mean pore size of 2.54 nm (Figure 2D). Uniform particle sizes with a controllable well-defined pore structure and a high specific surface area indicated that these nanomaterials could be a promising candidate for high-performance drug delivery.45


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)

Dynamic light scattering size (A) of HMSN and zeta potential (B) of tHMSN, pHMSN, HMSN-NH2, and HMSN (n=3).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

f3-ijn-10-1855: Dynamic light scattering size (A) of HMSN and zeta potential (B) of tHMSN, pHMSN, HMSN-NH2, and HMSN (n=3).Abbreviations: HMSN, hollow mesoporous silica nanoparticles; tHMSN, tLyp-1 and polyethylene glycol co-modified HMSN; pHMSN, polyethylene glycol-modified HMSN.
Mentions: Uniform and monodispersed SSN and HMSN were prepared following the method proposed by Fang et al37,38 with minor modifications. Transmission electron micrographs of the particles showed clearly that both SSN (Figure 2A) and HMSN (Figure 2B) had a spherical morphology and uniform particle size. The mean size of HMSN according to dynamic light scattering was 258.1±9.4 nm (n=3, Figure 3A), which was larger than the value obtained on transmission electron micrographs due to the presence of hydrated layers around the surfaces of the particles. Nitrogen adsorption– desorption isotherm measurements indicated that the HMSN had a relatively high specific surface area of 547.79 m2/g (Figure 2C) and a well-defined mean pore size of 2.54 nm (Figure 2D). Uniform particle sizes with a controllable well-defined pore structure and a high specific surface area indicated that these nanomaterials could be a promising candidate for high-performance drug delivery.45

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