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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

Schematic procedure for preparation of tLyp-1 and polyethylene glycol co-modified HMSN.Abbreviations: APTES, 3-aminopropyltriethoxysilane; CTAB, cetyltrimethylammonium bromide; HMSN, hollow mesoporous silica nanoparticles; SSN, solid SiO2 nanospheres; TEOS, tetraethyl orthosilicate; MAL-PEG2000-NHS, maleimido-PEG2000-N-hydroxysuccinimide.
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f1-ijn-10-1855: Schematic procedure for preparation of tLyp-1 and polyethylene glycol co-modified HMSN.Abbreviations: APTES, 3-aminopropyltriethoxysilane; CTAB, cetyltrimethylammonium bromide; HMSN, hollow mesoporous silica nanoparticles; SSN, solid SiO2 nanospheres; TEOS, tetraethyl orthosilicate; MAL-PEG2000-NHS, maleimido-PEG2000-N-hydroxysuccinimide.

Mentions: The synthesis of HMSN, PEG-HMSN (pHMSN), and tHMSN is shown in Figure 1. The synthesis process used for HMSN followed that of previous reports37,38 with slight modifications. Broadly, the process consisted of three steps, as follows: first, solid SiO2 nanospheres (SSN) were prepared via a sol-gel process using a modified Stöber method. Briefly, 74 mL of ethanol, 3.15 mL of aqueous ammonia solution (26%–28%), and 10 mL of ultrapure water were mixed and heated to 50°C, at which point 6 mL of tetraethyl orthosilicate was added rapidly. After 3 hours of reaction at 50°C, SSN were obtained by centrifugation and washed repeatedly with ultrapure water and ethanol. Second, 50 mg of SSN were homogeneously dispersed in a 1:2 (v/v) ethanol/water mixture, and 75 mg of CTAB, 300 μL of aqueous ammonia solution (26%–28%), and 125 μL of tetraethyl orthosilicate were added successively to the above mixture. After 12 hours of reaction at room temperature, the formed solid core-shell nanoparticles, denoted SSN@CTAB/SiO2, were centrifugally separated from the suspension and washed with ultrapure water. Third, 100 mg of SSN@CTAB/SiO2 nanomaterials were dispersed in 20 mL of water and heated to 50°C. Next, 464 mg of Na2CO3 was added into the mixture. The reaction was allowed to react for 11 hours at 50°C before the acquired HMSN structures were harvested by centrifugation. To remove the surfactant template in the shell of the HMSN, the products were dispersed in 120 mL of NH4NO3 ethanol solution (10 mg/mL). The mixture was heated to 45°C and stirred for 10 hours. The silica particles were centrifugally separated from the suspension and finally dispersed in dimethyl sulfoxide for further use.


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)

Schematic procedure for preparation of tLyp-1 and polyethylene glycol co-modified HMSN.Abbreviations: APTES, 3-aminopropyltriethoxysilane; CTAB, cetyltrimethylammonium bromide; HMSN, hollow mesoporous silica nanoparticles; SSN, solid SiO2 nanospheres; TEOS, tetraethyl orthosilicate; MAL-PEG2000-NHS, maleimido-PEG2000-N-hydroxysuccinimide.
© Copyright Policy
Related In: Results  -  Collection

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

f1-ijn-10-1855: Schematic procedure for preparation of tLyp-1 and polyethylene glycol co-modified HMSN.Abbreviations: APTES, 3-aminopropyltriethoxysilane; CTAB, cetyltrimethylammonium bromide; HMSN, hollow mesoporous silica nanoparticles; SSN, solid SiO2 nanospheres; TEOS, tetraethyl orthosilicate; MAL-PEG2000-NHS, maleimido-PEG2000-N-hydroxysuccinimide.
Mentions: The synthesis of HMSN, PEG-HMSN (pHMSN), and tHMSN is shown in Figure 1. The synthesis process used for HMSN followed that of previous reports37,38 with slight modifications. Broadly, the process consisted of three steps, as follows: first, solid SiO2 nanospheres (SSN) were prepared via a sol-gel process using a modified Stöber method. Briefly, 74 mL of ethanol, 3.15 mL of aqueous ammonia solution (26%–28%), and 10 mL of ultrapure water were mixed and heated to 50°C, at which point 6 mL of tetraethyl orthosilicate was added rapidly. After 3 hours of reaction at 50°C, SSN were obtained by centrifugation and washed repeatedly with ultrapure water and ethanol. Second, 50 mg of SSN were homogeneously dispersed in a 1:2 (v/v) ethanol/water mixture, and 75 mg of CTAB, 300 μL of aqueous ammonia solution (26%–28%), and 125 μL of tetraethyl orthosilicate were added successively to the above mixture. After 12 hours of reaction at room temperature, the formed solid core-shell nanoparticles, denoted SSN@CTAB/SiO2, were centrifugally separated from the suspension and washed with ultrapure water. Third, 100 mg of SSN@CTAB/SiO2 nanomaterials were dispersed in 20 mL of water and heated to 50°C. Next, 464 mg of Na2CO3 was added into the mixture. The reaction was allowed to react for 11 hours at 50°C before the acquired HMSN structures were harvested by centrifugation. To remove the surfactant template in the shell of the HMSN, the products were dispersed in 120 mL of NH4NO3 ethanol solution (10 mg/mL). The mixture was heated to 45°C and stirred for 10 hours. The silica particles were centrifugally separated from the suspension and finally dispersed in dimethyl sulfoxide for further use.

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