Safety Profiles and Antitumor Efficacy of Oncolytic Adenovirus Coated with Bioreducible Polymer in the Treatment of a CAR Negative Tumor Model
DC Field | Value | Language |
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dc.contributor.author | Jung, Soo-Jung | - |
dc.contributor.author | Kasala, Dayananda | - |
dc.contributor.author | Choi, Joung-Woo | - |
dc.contributor.author | Lee, Soo-Hwan | - |
dc.contributor.author | Hwang, June Kyu | - |
dc.contributor.author | Kim, Sung Wan | - |
dc.contributor.author | Yun, Chae-Ok | - |
dc.date.accessioned | 2021-08-02T18:27:24Z | - |
dc.date.available | 2021-08-02T18:27:24Z | - |
dc.date.created | 2021-05-12 | - |
dc.date.issued | 2015-01 | - |
dc.identifier.issn | 1525-7797 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/25671 | - |
dc.description.abstract | Adenovirus (Ad) vectors show promise as cancer gene therapy delivery vehicles, but immunogenic safety concerns and coxsackie and adenovirus receptor (CAR)-dependency have limited their use. Alternately, biocompatible and bioreducible nonviral vectors, including arginine-grafted cationic polymers, have been shown to deliver nucleic acids through a cell penetration peptide (CPP) and protein transduction domain (PTD) effect. We utilized the advantages of both viral and nonviral vectors to develop a hybrid gene delivery vehicle by coating Ad with mPEG-PEI-g-Arg-S-S-Arg-g-PEI-mPEG (Ad/PPSA). Characterization of Ad/PPSA particle size and zeta potential showed an overall size and cationic charge increase in a polymer concentration-dependent manner. Ad/PPSA also showed a marked transduction efficiency increase in both CAR-negative and -positive cells compared to naked Ad. Competition assays demonstrated that Ad/PPSA produced higher transgene expression levels than naked Ad and achieved CAR-independent transduction. Oncolytic Ad (DWP418)/PPSA was able to overcome the nonspecificity of polymer-only therapies by demonstrating cancer-specific killing effects. Furthermore, the DWP418/PPSA nanocomplex elicited a 2.24-fold greater antitumor efficacy than naked Ad in vivo. This was supported by immunohistochemical confirmation of Ad E1As accumulation in MCF7 xenografted tumors. Lastly, intravenous injection of DWP418/PPSA elicited less innate immune response compared to naked Ad, evaluated by interleukin-6 cytokine release into the serum. The increased antitumor effect and improved vector targeting to both CAR-negative and -positive cells make DWP418/PPSA a promising tool for cancer gene therapy. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | AMER CHEMICAL SOC | - |
dc.title | Safety Profiles and Antitumor Efficacy of Oncolytic Adenovirus Coated with Bioreducible Polymer in the Treatment of a CAR Negative Tumor Model | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Yun, Chae-Ok | - |
dc.identifier.doi | 10.1021/bm501116x | - |
dc.identifier.scopusid | 2-s2.0-84920896664 | - |
dc.identifier.wosid | 000347864200007 | - |
dc.identifier.bibliographicCitation | BIOMACROMOLECULES, v.16, no.1, pp.87 - 96 | - |
dc.relation.isPartOf | BIOMACROMOLECULES | - |
dc.citation.title | BIOMACROMOLECULES | - |
dc.citation.volume | 16 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 87 | - |
dc.citation.endPage | 96 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalResearchArea | Polymer Science | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Organic | - |
dc.relation.journalWebOfScienceCategory | Polymer Science | - |
dc.subject.keywordPlus | CELL-PENETRATING PEPTIDES | - |
dc.subject.keywordPlus | MEDIATED INTRACELLULAR DELIVERY | - |
dc.subject.keywordPlus | GENE DELIVERY | - |
dc.subject.keywordPlus | RECEPTOR EXPRESSION | - |
dc.subject.keywordPlus | POLY(AMIDO AMINE)S | - |
dc.subject.keywordPlus | PAMAM DENDRIMERS | - |
dc.subject.keywordPlus | DRUG-DELIVERY | - |
dc.subject.keywordPlus | COXSACKIE | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | THERAPY | - |
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