Versatile Types of MRI-Visible Cationic Nanoparticles Involving Pullulan Polysaccharides for Multifunctional Gene Carriers

Huang, Yajun; Hu, Hao; Li, Rui-Quan; Yu, Bingran; Xu, Fu‐Jian

doi:10.1021/acsami.5b11016

Cited by 43 publications

(49 citation statements)

References 50 publications

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“…The structures of polysaccharides vary considerably but span from linear to highly branched polymers with molecular weights ranging from thousands to millions, composed of mono‐ or disaccharides, or short‐chain oligomers bound together by glycosidic linkages . There is a rich history of research on the use of polysaccharides in a range of therapeutic applications including: i) soft tissue engineering, where the materials can be designed to mimic the mechanical properties of the extracellular matrix in the tissue; ii) as drug, protein, or gene delivery systems, where polysaccharides have a large number of reactive groups that allow for tunable properties such as pH‐responsiveness; and iii) as nanoprobes for cellular and tissue imaging . Of the available polysaccharides, the most studied biopolymers for use as therapeutic materials are arguably derivatives or composites of cellulose, chitosan, hyaluronic acid, and/or alginate .…”

Section: Introductionmentioning

confidence: 99%

Glycogen as a Building Block for Advanced Biological Materials

2019

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complex drug delivery systems that are challenging to scale up and therefore have limited clinical and commercial translation. Although numerous nanoparticles have been widely developed and used for various applications, including biomedical applications, [2] there is a growing interest in nontoxic and degradable alternatives to first-generation synthetic nanomaterials. Ideally the synthesis of such nanoparticles needs to be cost effective, simple, green, reproducible, scalable, and the constitutive building blocks of the nanoparticles should be nontoxic, functional, biodegradable, and available on a large scale. Naturally occurring nanoparticles could be such a valid alternative. These nanoparticles include intracellular structures, such as magnetosomes [3] and glycogen, and extracellular assemblies such as lipoproteins and viruses. [3] Among these, glycogen is the most abundant and versatile biological nanoparticle, which fulfils the requirements for the fabrication of nanostructured biomaterials. Glycogen is nature's prime nanoparticle that exists in most organisms, from bacteria and archaea to humans, [4,5] as a vital component of the cellular energy machinery. It is a highly branched polysaccharide comprising repeating units of glucose connected by linear α-d-(1,4) glycosidic linkages with α-d-(1,6) branching, structured into roughly spherical nanoparticles that have a high water solubility and molecular weight.The use of polysaccharides as components for advanced materials has been an attractive concept for decades. [6,7] A key motive is that polysaccharides, as a natural biomaterial, are endowed with a level of biodegradability and biocompatibility. In addition, they can be easily modified chemically or biochemically to produce functional derivatives, which are important for various therapeutic applications. [8] The structures of polysaccharides vary considerably but span from linear to highly branched polymers with molecular weights ranging from thousands to millions, composed of mono-or disaccharides, or short-chain oligomers bound together by glycosidic linkages. [9] There is a rich history of research on the use of polysaccharides in a range of therapeutic applications including: i) soft tissue engineering, [10,11] where the materials can be designed to mimic the mechanical properties of the extracellular matrix in the tissue; ii) as drug, protein, or gene delivery systems, [7,12,13] where polysaccharides have a large number of reactive groups [14] that allow for tunable properties [12] such as pH-responsiveness; [15] and iii) as nanoprobes for cellular Biological nanoparticles found in living systems possess distinct molecular architectures and diverse functions. Glycogen is a unique biological polysaccharide nanoparticle fabricated by nature through a bottom-up approach. The biocatalytic synthesis of glycogen has evolved over time to form a nanometer-sized dendrimer-like structure (20-150 nm) with a highly branched surface and a dense core. This makes glycogen markedly different from other natur...

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Section: Introductionmentioning

confidence: 99%

Glycogen as a Building Block for Advanced Biological Materials

2019

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“…Due to its liver specificity, pullulan was widely exploited for liver‐targeting drug or gene delivery . In our previous study, we observed pullulan‐containing vectors could effectively mediate gene delivery in liver cells . Herein, we investigated whether there was in vivo liver specificity for pullulan‐containing PuPGEA2 in mice.…”

Section: Resultsmentioning

confidence: 97%

“…The reaction time was adjusted to obtain different molecular weight PuPGMAs (Table S1, Supporting Information). The final PuPGEA products were harvested via ring‐opening reaction of PuPGMA with excess EA at 50 °C for 48 h. All the above synthesis procedures were described in detail previously . PuPGEAs with two molecular weights are denoted as PuPGEA1 and PuPGEA2, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Among these polysaccharides, pullulan has an inherent specificity for liver targeting and does not induce toxicity, immunogenicity, mutagenicity or carcinogenicity . Pullulan‐containing polyamines have also been shown to be able to effectively mediate gene delivery in liver cells such as HepG2 cells . This study provides a promising concept to codeliver lncRNA and pDNA for cancer therapy.…”

Section: Introductionmentioning

confidence: 91%

“…Herein, for a proof‐of‐concept, the pcDNA‐MEG3 and pcDNA‐P53 plasmids‐condensed nanocomplexes with PuPGEA vectors consisting of pullulan backbones and PGEA side chains were prepared to co‐deliver lncRNA and pDNA to treat HCC ( Figure A). Different PuPGEA vectors were first prepared by combination of atom transfer radical polymerization (ATRP) and epoxide ring‐opening reactions based on previous reports . The resultant PuPGEA/MEG3, PuPGEA/P53, and PuPGEA/(MEG3+P53) nanocomplexes formed via electrostatic interactions were examined for their tumor inhibition effects in vitro and in vivo HCC xenograft models.…”

Section: Introductionmentioning

confidence: 99%

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Effective Codelivery of lncRNA and pDNA by Pullulan‐Based Nanovectors for Promising Therapy of Hepatocellular Carcinoma

Ren

Cai

et al. 2016

Adv Funct Materials

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Hepatocellular carcinoma (HCC) is one of the most common cancers. Maternally expressed gene 3 (MEG3, one kind of long noncoding RNA [lncRNA]) can act as a tumor suppressor and regulate P53 target gene expression. However, lncRNA MEG3 demonstrates relatively low or no expression in human HCC. This study provides a promising concept to codeliver lncRNA and pDNA for cancer therapy. As proof‐of‐concept, the pcDNA‐MEG3 and pcDNA‐P53 plasmids‐condensed nanocomplexes with the liver‐targeting polycation gene vector, pullulan‐based ethanolamine‐modified poly(glycidyl methacrylate) (denoted as PuPGEA), are proposed to codeliver lncRNA and pDNA to treat HCC. Pullulan‐containing nanovectors are shown to be able to effectively mediate gene delivery in liver cells. To assess gene delivery performances of PuPGEA, a series of assays such as in vitro gene transfection, HCC cell proliferation, colony formation, migration, matrigel transwell assays, and in vivo xenograft animal models are carried out. The codelivery system with PuPGEA/(MEG3+P53) nanocomplexes demonstrates additive effects in suppressing HCC compared to PuPGEA/MEG3 or PuPGEA/P53 nanocomplexes alone. These results suggest that codelivery of lncRNA and pDNA by polycation nanovectors is a promising method to treat cancers.

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