Co-delivery of pretubulysin and siEG5 to EGFR overexpressing carcinoma cells.
Int J Pharm
; 569: 118570, 2019 Oct 05.
Article
em En
| MEDLINE
| ID: mdl-31352048
ABSTRACT
Small interfering RNA (siRNA) represents a new class of therapeutic agents. Its successful intracellular delivery is a major challenge. Lipo-oligomeric carriers can complex siRNA into lipopolyplexes and thus mediate its cellular uptake. In this study, siRNA against the kinesin related mRNA EG5 gene (siEG5) and the microtubule inhibitor pretubulysin (PT) were co-formulated into polyplexes using azide-containing lipo-oligomer 1198. Nanoparticles were further modified by click reaction using shielding agent DBCO-PEG or EGFR targeting peptide GE11 (DBCO-PEG-GE11). Polyplexes displayed efficient payload incorporation and homogenous particle sizes of 200â¯nm. The biological effects of the unmodified and surface-functionalized polyplexes were investigated. The successful GE11-mediated intracellular delivery of siRNA into the EGFR overexpressing KB and Huh7 cell lines facilitated potent silencing of an EGFP-luciferase reporter gene by GFP siRNA. Specific downregulation of EG5 mRNA by siEG5 resulted in the expected antitumoral activity. The combination formulation 1198 siEG5â¯+â¯PT provided superior antitumoral activity over free PT and 1198 siEG5.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
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Peptídeos
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Cinesinas
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RNA Interferente Pequeno
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Moduladores de Tubulina
Limite:
Humans
Idioma:
En
Revista:
Int J Pharm
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Alemanha