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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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ROI quantification and biodistribution studies.Time-activity curvesof the liver, U87MG tumor, blood, and muscle upon i.v. injection of(a) 64Cu-NOTA-MSN-PEG-VEGF121 (targeted group),and (b) 64Cu-NOTA-MSN-PEG (non-targeted group). (c) U87MGtumor uptake comparison between targeted and non-targeted groups.The difference between U87MG tumor uptake in targeted group and non-targetedgroup was statistically significant (**P < 0.01).(d) Ex vivo biodistribution study of two groups at 22 h p.i. (n = 3 for all groups).
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fig4: ROI quantification and biodistribution studies.Time-activity curvesof the liver, U87MG tumor, blood, and muscle upon i.v. injection of(a) 64Cu-NOTA-MSN-PEG-VEGF121 (targeted group),and (b) 64Cu-NOTA-MSN-PEG (non-targeted group). (c) U87MGtumor uptake comparison between targeted and non-targeted groups.The difference between U87MG tumor uptake in targeted group and non-targetedgroup was statistically significant (**P < 0.01).(d) Ex vivo biodistribution study of two groups at 22 h p.i. (n = 3 for all groups).

Mentions: Malignant glioblastomasare among the most angiogenic cancers, with VEGF being the dominantangiogenic mediator.36 To determine theVEGFR targeting efficacy and in vivo biodistribution patterns of as-synthesizednanoconjugates, serial whole body PET scans were carried out at multipletime-points (0.6, 3, 6 and 22 h postinjection [p.i.]). For this purpose,about 7.4–11.1 MBq of 64Cu-NOTA-MSN-PEG-VEGF121 and 64Cu-NOTA-MSN-PEG were intravenously injected(i.v.) in U87MG glioblastoma xenografted mice (n =3). Figure 3 shows the tumor (marked with anarrow) containing slices of the coronal PET images at various time-points.The data obtained from the region-of-interest (ROI) quantificationof the PET images is also presented in Figure 4A,B.


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)

ROI quantification and biodistribution studies.Time-activity curvesof the liver, U87MG tumor, blood, and muscle upon i.v. injection of(a) 64Cu-NOTA-MSN-PEG-VEGF121 (targeted group),and (b) 64Cu-NOTA-MSN-PEG (non-targeted group). (c) U87MGtumor uptake comparison between targeted and non-targeted groups.The difference between U87MG tumor uptake in targeted group and non-targetedgroup was statistically significant (**P < 0.01).(d) Ex vivo biodistribution study of two groups at 22 h p.i. (n = 3 for all groups).
© Copyright Policy
Related In: Results  -  Collection

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

fig4: ROI quantification and biodistribution studies.Time-activity curvesof the liver, U87MG tumor, blood, and muscle upon i.v. injection of(a) 64Cu-NOTA-MSN-PEG-VEGF121 (targeted group),and (b) 64Cu-NOTA-MSN-PEG (non-targeted group). (c) U87MGtumor uptake comparison between targeted and non-targeted groups.The difference between U87MG tumor uptake in targeted group and non-targetedgroup was statistically significant (**P < 0.01).(d) Ex vivo biodistribution study of two groups at 22 h p.i. (n = 3 for all groups).
Mentions: Malignant glioblastomasare among the most angiogenic cancers, with VEGF being the dominantangiogenic mediator.36 To determine theVEGFR targeting efficacy and in vivo biodistribution patterns of as-synthesizednanoconjugates, serial whole body PET scans were carried out at multipletime-points (0.6, 3, 6 and 22 h postinjection [p.i.]). For this purpose,about 7.4–11.1 MBq of 64Cu-NOTA-MSN-PEG-VEGF121 and 64Cu-NOTA-MSN-PEG were intravenously injected(i.v.) in U87MG glioblastoma xenografted mice (n =3). Figure 3 shows the tumor (marked with anarrow) containing slices of the coronal PET images at various time-points.The data obtained from the region-of-interest (ROI) quantificationof the PET images is also presented in Figure 4A,B.

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