Open Access<p>Local and systemic delivery of mRNA encoding survivin-T34A by lipoplex for efficient colon cancer gene therapy</p>
Author(s) -
Xueyan Zhang,
Ke Men,
Yuanfa Zhang,
Rui Zhang,
Li Yang,
Xingmei Duan
Publication year - 2019
Publication title -
international journal of nanomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.245
H-Index - 128
eISSN - 1178-2013
pISSN - 1176-9114
DOI - 10.2147/ijn.s198747
Subject(s) - survivin , genetic enhancement , systemic administration , gene delivery , protamine , messenger rna , cancer research , in vivo , transfection , cancer , cancer cell , in vitro , microbiology and biotechnology , medicine , biology , gene , biochemistry , heparin
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.