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Local and systemic delivery of mRNA encoding survivin-T34A by lipoplex for efficient colon cancer gene therapy

Background: In vitro transcribed (IVT) mRNA has been applied as an alternative therapeutic molecule to plasmid DNA in the field of cancer therapy and biomedical research studies. mRNA-based therapy has demonstrated several advantages over its DNA counterparts. However, its further therapeutic applic...

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Detalles Bibliográficos
Autores principales: Zhang, Xueyan, Men, Ke, Zhang, Yuanfa, Zhang, Rui, Yang, Li, Duan, Xingmei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503337/
https://www.ncbi.nlm.nih.gov/pubmed/31118608
http://dx.doi.org/10.2147/IJN.S198747
Descripción
Sumario:Background: In vitro transcribed (IVT) mRNA has been applied as an alternative therapeutic molecule to plasmid DNA in the field of cancer therapy and biomedical research studies. mRNA-based therapy has demonstrated several advantages over its DNA counterparts. However, its further therapeutic application is largely restricted by delivery method. Methods: In this work, a liposome-protamine lipoplex (CLPP) was prepared to deliver IVT mRNA encoding survivin-T34A gene, forming a novel core-shell structured nanoparticle formulation (CLPP/mSur-T34A). Results: The prepared CLPP/mSur-T34A particle had an average size of 186.1±3.1 nm, displaying high mRNA transfecting and expression efficiency on C26 tumor cells through lipid rafts-mediated endocytosis. CLPP/mSur-T34A mRNA formulation demonstrated obvious therapeutic effects on various models of C26 colon cancer both in vitro and in vivo. Particularly, local and systemic administration of CLPP/mSur-T34A particle exhibited superior antitumor effect regarding its DNA plasmid counterpart with high safety. Conclusion: Our results indicated the high delivery capacity of liposome-protamine lipoplex and further suggested CLPP/mSur-T34A mRNA formulation to be a potential candidate for colon cancer therapy.