RETRACTED ARTICLE: One-step Conjugation of Glycyrrhetinic Acid to Cationic Polymers for High-performance Gene Delivery to Cultured Liver Cell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...

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Main Authors: Yue Cong, Bingyang Shi, Yiqing Lu, Shihui Wen, Roger Chung, Dayong Jin
Format: Article
Language:English
Published: Nature Portfolio 2016-02-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/srep21891
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author Yue Cong
Bingyang Shi
Yiqing Lu
Shihui Wen
Roger Chung
Dayong Jin
author_facet Yue Cong
Bingyang Shi
Yiqing Lu
Shihui Wen
Roger Chung
Dayong Jin
author_sort Yue Cong
collection DOAJ
description 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,1H 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 (25kDa) 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.
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spelling doaj.art-d1d01828b5e14bf0af99b27c0eb88f132024-01-07T12:27:31ZengNature PortfolioScientific Reports2045-23222016-02-016111110.1038/srep21891RETRACTED ARTICLE: One-step Conjugation of Glycyrrhetinic Acid to Cationic Polymers for High-performance Gene Delivery to Cultured Liver CellYue Cong0Bingyang Shi1Yiqing Lu2Shihui Wen3Roger Chung4Dayong Jin5Institute of Pharmacy, Pharmaceutical College, Henan University, Jin Ming AvenueCollege of Life Sciences, Henan University, Jin Ming AvenueAdvanced Cytometry Labs, ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Macquarie UniversityAdvanced Cytometry Labs, ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Macquarie UniversityFaculty of Medicine & Health Sciences, Macquarie UniversityAdvanced Cytometry Labs, ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Macquarie UniversityAbstract 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,1H 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 (25kDa) 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.https://doi.org/10.1038/srep21891
spellingShingle Yue Cong
Bingyang Shi
Yiqing Lu
Shihui Wen
Roger Chung
Dayong Jin
RETRACTED ARTICLE: One-step Conjugation of Glycyrrhetinic Acid to Cationic Polymers for High-performance Gene Delivery to Cultured Liver Cell
Scientific Reports
title RETRACTED ARTICLE: One-step Conjugation of Glycyrrhetinic Acid to Cationic Polymers for High-performance Gene Delivery to Cultured Liver Cell
title_full RETRACTED ARTICLE: One-step Conjugation of Glycyrrhetinic Acid to Cationic Polymers for High-performance Gene Delivery to Cultured Liver Cell
title_fullStr RETRACTED ARTICLE: One-step Conjugation of Glycyrrhetinic Acid to Cationic Polymers for High-performance Gene Delivery to Cultured Liver Cell
title_full_unstemmed RETRACTED ARTICLE: One-step Conjugation of Glycyrrhetinic Acid to Cationic Polymers for High-performance Gene Delivery to Cultured Liver Cell
title_short RETRACTED ARTICLE: One-step Conjugation of Glycyrrhetinic Acid to Cationic Polymers for High-performance Gene Delivery to Cultured Liver Cell
title_sort retracted article one step conjugation of glycyrrhetinic acid to cationic polymers for high performance gene delivery to cultured liver cell
url https://doi.org/10.1038/srep21891
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