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

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.

SUBMITTER: Goel S

PROVIDER: S-EPMC4262629 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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

Goel Shreya S Chen Feng F Hong Hao H Valdovinos Hector F HF Hernandez Reinier R Shi Sixiang S Barnhart Todd E TE Cai Weibo W

ACS applied materials & interfaces 20141110 23

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 ...[more]

PMID: 25353068

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Project description:IntroductionLong-term stability of therapeutic candidates is necessary toward their clinical applications. For most nanoparticle systems formulated in aqueous solutions, lyophilization or freeze-drying is a common method to ensure long-term stability. While lyophilization of lipid, polymeric, or inorganic nanoparticles have been studied, little has been reported on lyophilization and stability of hybrid nanoparticle systems, consisting of polymers, inorganic particles, and antibody. Lyophilization of complex nanoparticle systems can be challenging with respect to preserving physicochemical properties and the biological activities of the materials. We recently reported an effective small-interfering RNA (siRNA) nanoparticle carrier consisting of 50-nm mesoporous silica nanoparticles decorated with a copolymer of polyethylenimine and polyethyleneglycol, and antibody.Materials and methodsToward future personalized medicine, the nanoparticle carriers were lyophilized alone and loaded with siRNA upon reconstitution by a few minutes of simple mixing in phosphate-buffered saline. Herein, we optimize the lyophilization of the nanoparticles in terms of buffers, lyoprotectants, reconstitution, and time and temperature of freezing and drying steps, and monitor the physical and chemical properties (reconstitution, hydrodynamic size, charge, and siRNA loading) and biological activities (gene silencing, cancer cell killing) of the materials after storing at various temperatures and times.ResultsThe material was best formulated in Tris-HCl buffer with 5% w/w trehalose. Freezing step was performed at -55°C for 3 h, followed by a primary drying step at -40°C (100 µBar) for 24 h and a secondary drying step at 20°C (20 µBar) for 12 h. The lyophilized material can be stored stably for 2 months at 4°C and at least 6 months at -20°C.ConclusionWe successfully developed the lyophilization process that should be applicable to other similar nanoparticle systems consisting of inorganic nanoparticle cores modified with cationic polymers, PEG, and antibodies.

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

Publications

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

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