Synthesis and characterization of a pH-sensitive shielding system for polycation gene carriers

Xia, Jiangzhou; Chen, Jie; Tian, Huayu; Chen, Xuesi

doi:10.1007/s11426-010-0108-x

Cited by 25 publications

(20 citation statements)

References 16 publications

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“…N-carboxyanhydride of b-benzyl-L-aspartate (BLA-NCA) and N-carboxyanhydride of e-benzyloxycarbonyl-L-lysine (Lys(Z)-NCA) were synthesized according to our previously reported method [25]. Poly(L-glutamic acid) (PLG) was prepared according to our previously reported method [26]. Dichloromethane (DCM) was refluxed with sodium and distilled under nitrogen prior to use.…”

Section: Methodsmentioning

confidence: 99%

Charge-conversional zwitterionic copolymer as pH-sensitive shielding system for effective tumor treatment

et al. 2015

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Section: Methodsmentioning

confidence: 99%

Charge-conversional zwitterionic copolymer as pH-sensitive shielding system for effective tumor treatment

et al. 2015

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“…), are considered as the most promising materials for biomedical applications including drug delivery, gene delivery and imaging. To increase the in vivo stability of polycation gene carriers, Chen's group [21] synthesized a pH-sensitive shielding system, γ-benzyll-glutamate-co-glutamate acid polymer (PGA(60)). This compound showed pH sensitivity at about pH 6.0, and could efficiently shield the positive charge of DNA/PEI complexes.…”

Section: Polypeptide Based Vectorsmentioning

confidence: 99%

Current progress of polymeric gene vectors

Zhang

Sun

Zhuo

et al. 2011

Sci. China Life Sci.

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After over 40 years of progress, gene therapy provides great opportunities for treating diseases from various genetic disorders, infections and cancers. The success of gene therapy largely depends on the availability of suitable gene vectors. As an attractive alternative to virus-based gene therapy, non-viral gene delivery system has been developed and investigated due to their merits including low immunogenecity, convenient operability, and large-scale manufacturability [1]. Because polycations can condense with DNA as a result of electrostatic interactions, form nanosize polyplexes, and protect DNA from degradation by DNase, cationic polymer becomes a major type of non-viral gene delivery vectors ( Figure 1) [2]. A wide range of polymeric vectors have been developed and investigated in the past decade, such as polyethylenimine (PEI)-based vectors, poly(L-lysine) (PLL)-based vectors, dendrimer-based vectors, polypeptide-based vectors, and chitosan-based vectors [3]. However, unlike viral vectors that have the ability to infect host cells and overcome cellular barriers through the course of evolution, nonviral gene vectors exhibit significantly reduced transfection efficiency as they are obstructed by various extra-and intracellular barriers, including serum proteins in blood stream, cell membrane, endosomal compartment and nuclear membrane [4].As a result, numerous studies have focused on designing polymer carriers that have smart molecular structure, present good biocompatibility, avoid both in vitro and in vivo barriers, and achieve successful delivery of genetic material [1]. To circumvent different systemic and cellular obstacles Figure 1 Three main strategies employed to package DNA [4].during gene delivery, proper functional groups were conjugated to polymeric vectors. The current modification of polymeric vectors has shown great improvements in enhancing intracellular gene transfer efficiency and attaining tumor targeted gene delivery [4]. For example, receptormediated cell uptake can quickly deliver ligand-targeted polyplexes into endosomes, membrane active compounds (lipids and peptides) can enhance the release of endocytosed materials. Moreover, nuclear localization signal peptides can enhance both the nuclear transport and expression of DNA. Here, current research progress regarding polymeric gene vectors that mainly published in Chinese magazines from 2010 was reviewed, and future trends for the polymer-based gene delivery systems would also be delineated.

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“…Branched PEI contained various levels of primary, secondary and tertiary amines that could be protonated under a range of pH, giving rise to the so-called "proton sponge" effect, which could prevent the DNA from endosomal disruption [16,17]. Studies showed that the gene transfection efficiency and cytotoxicity are closely associated with PEI's molecular weight [18,20]. High molecular weight PEI, such as PEI 25 K with non-degradable backbone and high cationic charge density, shows high efficiency for gene transfection, however, with high cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Bioreducible crosslinked low molecular weight branched PEI-PBLG as an efficient gene carrier

et al. 2010

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Low molecular weight polyethylenimine-poly(gamma-benzyl L-glutamate) (PEI-PBLG) was crosslinked by N,N′-cystaminebisacrylamide (CBA) to get the polymer named as CBA-PEI-PBLG (CPP). CPP not only inherits PEI-PBLG's amphiphilic advantages, but also possesses reducible properties. CPP can complex with DNA to form nanoparticles. CPP/DNA complex particles were characterized by particle size and zeta potential analysis. The result showed that the complex particles have suitable size and surface charges for gene delivery. And gel retardation assay also prove CBA-PEI-PBLG has proper condensing ability for DNA. CPP has good reducible property, and also has good biocompatibility because of introducing PBLG segment. The cytotoxicity of CPP was evaluated using MTT assay, and the results showed CPP has lower cytotoxicity compared with PEI 25 K. The transfection properties were characterized in different cells by using plasmid DNA as a reporter. CPP showed higher transfection efficiencies and lower cytotoxicity in HeLa cells. This was attributed to bioreducible and biocompatibility properties of the CPP. These results suggested that CPP is a promising low-toxic, highly effective non-viral gene carrier.

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Synthesis and characterization of a pH-sensitive shielding system for polycation gene carriers

Cited by 25 publications

References 16 publications

Charge-conversional zwitterionic copolymer as pH-sensitive shielding system for effective tumor treatment

Charge-conversional zwitterionic copolymer as pH-sensitive shielding system for effective tumor treatment

Current progress of polymeric gene vectors

Bioreducible crosslinked low molecular weight branched PEI-PBLG as an efficient gene carrier

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