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VEGF₁₂₁-conjugated mesoporous silica nanoparticle: a tumor targeted drug delivery system.

Goel S, Chen F, Hong H, Valdovinos HF, Hernandez R, Shi S, Barnhart TE, Cai W - ACS Appl Mater Interfaces (2014)

Bottom Line: Although a number of anti-VEGFR therapies have been conceived, inefficient drug administration still limits their therapeutic efficacy and raises concerns of potential side effects.Our results demonstrated that a significantly higher amount of sunitinib could be delivered to the U87MG tumor by targeting VEGFR when compared with the non-targeted counterparts.The as-developed VEGF121-conjugated MSN could become another attractive nanoplatform for the design of future theranostic nanomedicine.

View Article: PubMed Central - PubMed

Affiliation: Materials Science Program, University of Wisconsin-Madison , Madison, Wisconsin 53705, United States.

ABSTRACT
The vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) signaling cascade plays a critical role in tumor angiogenesis and metastasis and has been correlated with several poorly prognostic cancers such as malignant gliomas. Although a number of anti-VEGFR therapies have been conceived, inefficient drug administration still limits their therapeutic efficacy and raises concerns of potential side effects. In the present work, we propose the use of uniform mesoporous silica nanoparticles (MSNs) for VEGFR targeted positron emission tomography imaging and delivery of the anti-VEGFR drug (i.e., sunitinib) in human glioblastoma (U87MG) bearing murine models. MSNs were synthesized, characterized and modified with polyethylene glycol, anti-VEGFR ligand VEGF121 and radioisotope (64)Cu, followed by extensive in vitro, in vivo and ex vivo studies. Our results demonstrated that a significantly higher amount of sunitinib could be delivered to the U87MG tumor by targeting VEGFR when compared with the non-targeted counterparts. The as-developed VEGF121-conjugated MSN could become another attractive nanoplatform for the design of future theranostic nanomedicine.

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Related in: MedlinePlus

Ex vivohistology analysis. Immunofluorescence staining of thetissue slices with CD31 (red, with antimouse CD31 primary antibody;left panel). Fluorescein conjugated MSN nanoconjugates (green, middlepanel). Merged images are also shown at the right panel. Scale bar:100 μm.
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fig5: Ex vivohistology analysis. Immunofluorescence staining of thetissue slices with CD31 (red, with antimouse CD31 primary antibody;left panel). Fluorescein conjugated MSN nanoconjugates (green, middlepanel). Merged images are also shown at the right panel. Scale bar:100 μm.

Mentions: Frozen tissueslices (6 μm thick) were stained for vascular endothelial markerCD31, using rat antimouse CD31 primary antibody and Cy3 labeled donkeyantirat secondary antibody using a previously reported protocol.39 The stained slices were observed using a NikonEclipse Ti microscope. The green fluorescence from fluorescein inFigure 5 indicates the location of the nanoparticlesand the red fluorescence marks the position of the vessels. Excellentoverlay of the red and green signals in the U87MG tumor of the targetedgroup indicates the vasculature specific uptake of MSN-PEG-VEGF121 with little extravasation. Consistent with PET imagingand biodistribution studies, significant green signals were observedin both the liver and spleen tissue slices, indicating high nanoparticleuptake in these organs. However, very weak overlap was observed betweenthe red and green fluorescence signals, indicating the nonspecificnature of the nanoparticle accumulation in these organs, due to themacrophage capture or other mechanisms. As expected, no significantgreen fluorescence was observed in muscle tissue, which correlatedwell with the PET findings. Overall, our ex vivo histological analysisof the tissues further confirms the VEGFR specific uptake of our nanoconjugates.


VEGF₁₂₁-conjugated mesoporous silica nanoparticle: a tumor targeted drug delivery system.

Goel S, Chen F, Hong H, Valdovinos HF, Hernandez R, Shi S, Barnhart TE, Cai W - ACS Appl Mater Interfaces (2014)

Ex vivohistology analysis. Immunofluorescence staining of thetissue slices with CD31 (red, with antimouse CD31 primary antibody;left panel). Fluorescein conjugated MSN nanoconjugates (green, middlepanel). Merged images are also shown at the right panel. Scale bar:100 μm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4262629&req=5

fig5: Ex vivohistology analysis. Immunofluorescence staining of thetissue slices with CD31 (red, with antimouse CD31 primary antibody;left panel). Fluorescein conjugated MSN nanoconjugates (green, middlepanel). Merged images are also shown at the right panel. Scale bar:100 μm.
Mentions: Frozen tissueslices (6 μm thick) were stained for vascular endothelial markerCD31, using rat antimouse CD31 primary antibody and Cy3 labeled donkeyantirat secondary antibody using a previously reported protocol.39 The stained slices were observed using a NikonEclipse Ti microscope. The green fluorescence from fluorescein inFigure 5 indicates the location of the nanoparticlesand the red fluorescence marks the position of the vessels. Excellentoverlay of the red and green signals in the U87MG tumor of the targetedgroup indicates the vasculature specific uptake of MSN-PEG-VEGF121 with little extravasation. Consistent with PET imagingand biodistribution studies, significant green signals were observedin both the liver and spleen tissue slices, indicating high nanoparticleuptake in these organs. However, very weak overlap was observed betweenthe red and green fluorescence signals, indicating the nonspecificnature of the nanoparticle accumulation in these organs, due to themacrophage capture or other mechanisms. As expected, no significantgreen fluorescence was observed in muscle tissue, which correlatedwell with the PET findings. Overall, our ex vivo histological analysisof the tissues further confirms the VEGFR specific uptake of our nanoconjugates.

Bottom Line: Although a number of anti-VEGFR therapies have been conceived, inefficient drug administration still limits their therapeutic efficacy and raises concerns of potential side effects.Our results demonstrated that a significantly higher amount of sunitinib could be delivered to the U87MG tumor by targeting VEGFR when compared with the non-targeted counterparts.The as-developed VEGF121-conjugated MSN could become another attractive nanoplatform for the design of future theranostic nanomedicine.

View Article: PubMed Central - PubMed

Affiliation: Materials Science Program, University of Wisconsin-Madison , Madison, Wisconsin 53705, United States.

ABSTRACT
The vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) signaling cascade plays a critical role in tumor angiogenesis and metastasis and has been correlated with several poorly prognostic cancers such as malignant gliomas. Although a number of anti-VEGFR therapies have been conceived, inefficient drug administration still limits their therapeutic efficacy and raises concerns of potential side effects. In the present work, we propose the use of uniform mesoporous silica nanoparticles (MSNs) for VEGFR targeted positron emission tomography imaging and delivery of the anti-VEGFR drug (i.e., sunitinib) in human glioblastoma (U87MG) bearing murine models. MSNs were synthesized, characterized and modified with polyethylene glycol, anti-VEGFR ligand VEGF121 and radioisotope (64)Cu, followed by extensive in vitro, in vivo and ex vivo studies. Our results demonstrated that a significantly higher amount of sunitinib could be delivered to the U87MG tumor by targeting VEGFR when compared with the non-targeted counterparts. The as-developed VEGF121-conjugated MSN could become another attractive nanoplatform for the design of future theranostic nanomedicine.

Show MeSH
Related in: MedlinePlus