title: One-step Conjugation of Glycyrrhetinic Acid to Cationic Polymers for High-performance Gene Delivery to Cultured Liver Cell.
abstract: Gene therapies represent a promising therapeutic route for liver cancers, but major challenges remain in the design of safe and efficient gene-targeting delivery systems. For example, cationic polymers show good transfection efficiency as gene carriers, but are hindered by cytotoxicity and non-specific targeting. Here we report a versatile method of one-step conjugation of glycyrrhetinic acid (GA) to reduce cytotoxicity and improve the cultured liver cell -targeting capability of cationic polymers. We have explored a series of cationic polymer derivatives by coupling different ratios of GA to polypropylenimine (PPI) dendrimer. These new gene carriers (GA-PPI dendrimer) were systematically characterized by UV-vis,(1)H NMR titration, electron microscopy, zeta potential, dynamic light-scattering, gel electrophoresis, confocal microscopy and flow cytometry. We demonstrate that GA-PPI dendrimers can efficiently load and protect pDNA, via formation of nanostructured GA-PPI/pDNA polyplexes. With optimal GA substitution degree (6.31%), GA-PPI dendrimers deliver higher liver cell transfection efficiency (43.5% vs 22.3%) and lower cytotoxicity (94.3% vs 62.5%, cell viability) than the commercial bench-mark DNA carrier bPEI (25 kDa) with cultured liver model cells (HepG2). There results suggest that our new GA-PPI dendrimer are a promising candidate gene carrier for targeted liver cancer therapy.
authors.affiliation: Institute of Pharmacy, Pharmaceutical College, Henan University, Jin Ming Avenue, Kaifeng, Henan, 475004, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Cong
authors.affiliation: College of Life Sciences, Henan University, Jin Ming Avenue, Kaifeng, Henan, 475004, China.|Advanced Cytometry Labs, ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Macquarie University, Sydney, NSW, 2109, Australia.|Faculty of Medicine &Health Sciences, Macquarie University, Sydney, NSW, 2109, Australia.
authors.forename: Bingyang
authors.initials: B
authors.lastname: Shi
authors.affiliation: Advanced Cytometry Labs, ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Macquarie University, Sydney, NSW, 2109, Australia.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Advanced Cytometry Labs, ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Macquarie University, Sydney, NSW, 2109, Australia.
authors.forename: Shihui
authors.initials: S
authors.lastname: Wen
authors.affiliation: Faculty of Medicine &Health Sciences, Macquarie University, Sydney, NSW, 2109, Australia.
authors.forename: Roger
authors.initials: R
authors.lastname: Chung
authors.affiliation: Advanced Cytometry Labs, ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Macquarie University, Sydney, NSW, 2109, Australia.
authors.forename: Dayong
authors.initials: D
authors.lastname: Jin
mesh_terms: D000818:Animals; D001692:Biological Transport; D016466:CHO Cells; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003412:Cricetulus; D050091:Dendrimers / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D018014:Gene Transfer Techniques; D006034:Glycyrrhetinic Acid / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053758:Nanoparticles; D010316:Particle Size; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism*; D011126:Polypropylenes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D050091:Dendrimers; D011126:Polypropylenes; C443641:poly(propyleneimine); D006034:Glycyrrhetinic Acid