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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

In vitro cumulative release of doxorubicin from pHMSN (b, c) and from tHMSN (a, d) in phosphate-buffered saline at pH 5.0 (a, b) or pH 7.4 (c, d) and 37°C.Notes: (B) Shows the data in (A) specifically for the first 12 hours (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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f5-ijn-10-1855: In vitro cumulative release of doxorubicin from pHMSN (b, c) and from tHMSN (a, d) in phosphate-buffered saline at pH 5.0 (a, b) or pH 7.4 (c, d) and 37°C.Notes: (B) Shows the data in (A) specifically for the first 12 hours (n=3).Abbreviations: HMSN, hollow mesoporous silica nanoparticles; tHMSN, tLyp-1 and polyethylene glycol co-modified HMSN; pHMSN, polyethylene glycol-modified HMSN.

Mentions: Typically, HMSN had a huge internal cavity and large specific surface area, ensuring a high drug loading capacity (LC). Not surprisingly, the LC of doxorubicin, a model hydrophobic drug, was calculated to be 29.5±1.3 wt%, 24.9±1.1 wt%, and 23.8±2.2 wt% for HMSN, pHMSN, and tHMSN, respectively (n=3). The drug-release profiles for the nanoparticles in neutral or acid PBS buffer were then investigated; similar biphasic patterns were seen, as characterized by fast initial release within the first 12 hours (Figure 5B) and slow continuous release in the subsequent 84 hours (Figure 5A). The rate of release of doxorubicin from the nanoparticles at pH 5.0 was clearly more rapid than that at pH 7.4. These results may be ascribed to the fact that the solubility of doxorubicin is significantly influenced by pH in aqueous medium. It is worth mentioning that such a characteristic (ie, pH-sensitive release of cargo) is very favorable in antitumor treatment given that the microenvironments of extracellular tissues of tumors and intracellular lysosomes and endosomes are acidic.46


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)

In vitro cumulative release of doxorubicin from pHMSN (b, c) and from tHMSN (a, d) in phosphate-buffered saline at pH 5.0 (a, b) or pH 7.4 (c, d) and 37°C.Notes: (B) Shows the data in (A) specifically for the first 12 hours (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

f5-ijn-10-1855: In vitro cumulative release of doxorubicin from pHMSN (b, c) and from tHMSN (a, d) in phosphate-buffered saline at pH 5.0 (a, b) or pH 7.4 (c, d) and 37°C.Notes: (B) Shows the data in (A) specifically for the first 12 hours (n=3).Abbreviations: HMSN, hollow mesoporous silica nanoparticles; tHMSN, tLyp-1 and polyethylene glycol co-modified HMSN; pHMSN, polyethylene glycol-modified HMSN.
Mentions: Typically, HMSN had a huge internal cavity and large specific surface area, ensuring a high drug loading capacity (LC). Not surprisingly, the LC of doxorubicin, a model hydrophobic drug, was calculated to be 29.5±1.3 wt%, 24.9±1.1 wt%, and 23.8±2.2 wt% for HMSN, pHMSN, and tHMSN, respectively (n=3). The drug-release profiles for the nanoparticles in neutral or acid PBS buffer were then investigated; similar biphasic patterns were seen, as characterized by fast initial release within the first 12 hours (Figure 5B) and slow continuous release in the subsequent 84 hours (Figure 5A). The rate of release of doxorubicin from the nanoparticles at pH 5.0 was clearly more rapid than that at pH 7.4. These results may be ascribed to the fact that the solubility of doxorubicin is significantly influenced by pH in aqueous medium. It is worth mentioning that such a characteristic (ie, pH-sensitive release of cargo) is very favorable in antitumor treatment given that the microenvironments of extracellular tissues of tumors and intracellular lysosomes and endosomes are acidic.46

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