Penetration and Silencing Activity of VEGF Dicer Substrate siRNA Vectorized by Chitosan Nanoparticles in Monolayer Culture and a Solid Tumor Model In Vitro for Potential Application in Tumor Therapy

Maria Abdul Ghafoor Raja, Haliza Katas, Zariyantey Abd Hamid

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Penetration and distribution of drug through the avascular regions of human solid tumors after extravasation are crucial concerns for antitumor efficacy. To address this issue, an in vitro solid tumor model of multicellular layers (MCLs) of human colorectal cancer cells (DLD-1) was established. In an attempt to deliver Dicer substrate small interfering RNA (DsiRNA), chitosan (CS) nanoparticles have been developed for targeting vascular endothelial growth factor (VEGF) gene for tumor growth inhibition. The DsiRNA-CS nanoparticles prepared by ionic gelation method had provided maximal protection of DsiRNA in full human serum up to 48 h incubation. RT-PCR studies revealed significant concentration- and time-dependent knock-down of VEGF mRNA and its product due to uniform penetration of DsiRNA-CS nanoparticles throughout MCLs. Taken together, this study also demonstrated that DsiRNA-CS nanoparticles could effectively knock down VEGF gene as therapeutic target in monolayer culture or in solid tumor model for potential treatment of human colorectal carcinoma.

Original languageEnglish
Article number7201204
JournalJournal of Nanomaterials
Volume2016
DOIs
Publication statusPublished - 2016

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Chitosan
RNA
Vascular Endothelial Growth Factor A
Small Interfering RNA
Tumors
Monolayers
Nanoparticles
Substrates
Genes
Gelation
Cell culture
Cells
Intercellular Signaling Peptides and Proteins
Messenger RNA
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Materials Science(all)

Cite this

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title = "Penetration and Silencing Activity of VEGF Dicer Substrate siRNA Vectorized by Chitosan Nanoparticles in Monolayer Culture and a Solid Tumor Model In Vitro for Potential Application in Tumor Therapy",
abstract = "Penetration and distribution of drug through the avascular regions of human solid tumors after extravasation are crucial concerns for antitumor efficacy. To address this issue, an in vitro solid tumor model of multicellular layers (MCLs) of human colorectal cancer cells (DLD-1) was established. In an attempt to deliver Dicer substrate small interfering RNA (DsiRNA), chitosan (CS) nanoparticles have been developed for targeting vascular endothelial growth factor (VEGF) gene for tumor growth inhibition. The DsiRNA-CS nanoparticles prepared by ionic gelation method had provided maximal protection of DsiRNA in full human serum up to 48 h incubation. RT-PCR studies revealed significant concentration- and time-dependent knock-down of VEGF mRNA and its product due to uniform penetration of DsiRNA-CS nanoparticles throughout MCLs. Taken together, this study also demonstrated that DsiRNA-CS nanoparticles could effectively knock down VEGF gene as therapeutic target in monolayer culture or in solid tumor model for potential treatment of human colorectal carcinoma.",
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AU - Raja, Maria Abdul Ghafoor

AU - Katas, Haliza

AU - Abd Hamid, Zariyantey

PY - 2016

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N2 - Penetration and distribution of drug through the avascular regions of human solid tumors after extravasation are crucial concerns for antitumor efficacy. To address this issue, an in vitro solid tumor model of multicellular layers (MCLs) of human colorectal cancer cells (DLD-1) was established. In an attempt to deliver Dicer substrate small interfering RNA (DsiRNA), chitosan (CS) nanoparticles have been developed for targeting vascular endothelial growth factor (VEGF) gene for tumor growth inhibition. The DsiRNA-CS nanoparticles prepared by ionic gelation method had provided maximal protection of DsiRNA in full human serum up to 48 h incubation. RT-PCR studies revealed significant concentration- and time-dependent knock-down of VEGF mRNA and its product due to uniform penetration of DsiRNA-CS nanoparticles throughout MCLs. Taken together, this study also demonstrated that DsiRNA-CS nanoparticles could effectively knock down VEGF gene as therapeutic target in monolayer culture or in solid tumor model for potential treatment of human colorectal carcinoma.

AB - Penetration and distribution of drug through the avascular regions of human solid tumors after extravasation are crucial concerns for antitumor efficacy. To address this issue, an in vitro solid tumor model of multicellular layers (MCLs) of human colorectal cancer cells (DLD-1) was established. In an attempt to deliver Dicer substrate small interfering RNA (DsiRNA), chitosan (CS) nanoparticles have been developed for targeting vascular endothelial growth factor (VEGF) gene for tumor growth inhibition. The DsiRNA-CS nanoparticles prepared by ionic gelation method had provided maximal protection of DsiRNA in full human serum up to 48 h incubation. RT-PCR studies revealed significant concentration- and time-dependent knock-down of VEGF mRNA and its product due to uniform penetration of DsiRNA-CS nanoparticles throughout MCLs. Taken together, this study also demonstrated that DsiRNA-CS nanoparticles could effectively knock down VEGF gene as therapeutic target in monolayer culture or in solid tumor model for potential treatment of human colorectal carcinoma.

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