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• W2607242519 endingPage "377" @default.
• W2607242519 startingPage "366" @default.
• W2607242519 abstract "Liposomes are an effective gene and/or drug delivery system, widely used in biomedical applications including gene therapy and chemotherapy. Here, we designed a photo-responsive liposome (lipVP) loaded with a photosensitizer verteporfin (VP). This photosensitizer is clinically approved for photodynamic therapy (PDT). LipVP was employed as a DNA carrier for pituitary adenylyl cyclase-activating polypeptide (PACAP) receptor 1 (PAC1R) gene knockdown in PC12 cells. This has been done by incorporating PAC1R antisense oligonucleotides inside the lipVP cavity. Cells that have taken up the lipVP were exposed to light from a UV light source. As a result of this exposure, reactive oxygen species (ROS) were generated from VP, destabilizing the endolysosomal membranes and enhancing the liposomal release of antisense DNA into the cytoplasm. Endolysosomal escape of DNA was documented at different time points based on quantitative analysis of colocalization between fluorescently labeled DNA and endosomes and lysosomes. The released antisense oligonucleotides were found to silence PAC1R mRNA. The efficiency of this photo-induced gene silencing was demonstrated by a 74% ± 5% decrease in PAC1R fluorescence intensity. Following the light-induced DNA transfer into cells, cell differentiation with exposure to two kinds of PACAP peptides was observed to determine the cell phenotypic change after PAC1R gene knockdown. Liposomes are an effective gene and/or drug delivery system, widely used in biomedical applications including gene therapy and chemotherapy. Here, we designed a photo-responsive liposome (lipVP) loaded with a photosensitizer verteporfin (VP). This photosensitizer is clinically approved for photodynamic therapy (PDT). LipVP was employed as a DNA carrier for pituitary adenylyl cyclase-activating polypeptide (PACAP) receptor 1 (PAC1R) gene knockdown in PC12 cells. This has been done by incorporating PAC1R antisense oligonucleotides inside the lipVP cavity. Cells that have taken up the lipVP were exposed to light from a UV light source. As a result of this exposure, reactive oxygen species (ROS) were generated from VP, destabilizing the endolysosomal membranes and enhancing the liposomal release of antisense DNA into the cytoplasm. Endolysosomal escape of DNA was documented at different time points based on quantitative analysis of colocalization between fluorescently labeled DNA and endosomes and lysosomes. The released antisense oligonucleotides were found to silence PAC1R mRNA. The efficiency of this photo-induced gene silencing was demonstrated by a 74% ± 5% decrease in PAC1R fluorescence intensity. Following the light-induced DNA transfer into cells, cell differentiation with exposure to two kinds of PACAP peptides was observed to determine the cell phenotypic change after PAC1R gene knockdown." @default.
• W2607242519 created "2017-04-28" @default.
• W2607242519 creator A5030443471 @default.
• W2607242519 creator A5050015844 @default.
• W2607242519 creator A5054791447 @default.
• W2607242519 date "2017-06-01" @default.
• W2607242519 modified "2023-09-27" @default.
• W2607242519 title "Light-Triggerable Liposomes for Enhanced Endolysosomal Escape and Gene Silencing in PC12 Cells" @default.
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• W2607242519 doi "https://doi.org/10.1016/j.omtn.2017.04.015" @default.
• W2607242519 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5423320" @default.
• W2607242519 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28624212" @default.
• W2607242519 hasPublicationYear "2017" @default.
• W2607242519 type Work @default.

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