Biodegradable nanoparticles composed of dendrigraft poly-l-lysine for gene delivery

Kodama, Yukinobu; Nakamura, Tadahiro; Kurosaki, Tomoaki; Egashira, Kanoko; Mine, Toyoharu; Nakagawa, Hiroo; Muro, Takahiro; Kitahara, Takashi; Higuchi, Norihide; Sasaki, Hidetada

doi:10.1016/j.ejpb.2014.04.013

Cited by 64 publications

(61 citation statements)

References 31 publications

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“…The toxicity is mainly caused by cations that can produce electrostatic attraction with anions on the surface of the cell membrane. 37 However, in the present study, this is not the case. The cationic amino groups have been blocked by covalent bonding of carboxyl groups on MNP-CA with amino groups on DGL.…”

Section: Results and Discussion Synthesis Of The Mnp-dgl-rgd-gx1-dox Npscontrasting

confidence: 54%

Heterogeneous dimer peptide-conjugated polylysine dendrimer-Fe3O4 composite as a novel nanoscale molecular probe for early diagnosis and therapy in hepatocellular carcinoma

Shen¹,

Li²,

Fan³

et al. 2017

IJN

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A novel nanoscale molecular probe is formulated in order to reduce toxicity and side effects of antitumor drug doxorubicin (DOX) in normal tissues and to enhance the detection sensitivity during early imaging diagnosis. The mechanism involves a specific targeting of Arg-Gly-Asp peptide (RGD)-GX1 heterogeneous dimer peptide-conjugated dendrigraft poly- l -lysine (DGL)–magnetic nanoparticle (MNP) composite by α v β 3 -integrin/vasculature endothelium receptor-mediated synergetic effect. The physicochemical properties of the nanoprobe were characterized by using transmission electron microscope, Fourier transform infrared spectroscopy, X-ray diffraction, dynamic light scattering (DLS), and vibrating sample magnetometer. The average diameter of the resulting MNP–DGL–RGD-GX1–DOX nanoparticles (NPs) was ~150−160 nm by DLS under simulate physiological medium. In the present experimental system, the loading amount of DOX on NPs accounted for 414.4 mg/g for MNP–DGL–RGD-GX1–DOX. The results of cytotoxicity, flow cytometry, and cellular uptake consistently indicated that the MNP–DGL–RGD-GX1–DOX NPs were inclined to target HepG2 cells in selected three kinds of cells. In vitro exploration of molecular mechanism revealed that cell apoptosis was associated with the overexpression of Fas protein and the significant activation of caspase-3. In vivo magnetic resonance imaging and biodistribution study showed that the MNP–DGL–RGD-GX1–DOX formulation had high affinity to the tumor tissue, leading to more aggregation of NPs in the tumor. In vivo antitumor efficacy research verified that MNP–DGL–RGD-GX1–DOX NPs possessed significant antitumor activity and the tumor inhibitory rate reached 78.5%. These results suggested that NPs could be promising in application to early diagnosis and therapy in hepatocellular carcinoma as a specific nanoprobe.

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Section: Results and Discussion Synthesis Of The Mnp-dgl-rgd-gx1-dox Npscontrasting

confidence: 54%

Heterogeneous dimer peptide-conjugated polylysine dendrimer-Fe3O4 composite as a novel nanoscale molecular probe for early diagnosis and therapy in hepatocellular carcinoma

Shen¹,

Li²,

Fan³

et al. 2017

IJN

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“…Among the polymers commonly employed as non-viral si-RNA delivery systems, chitosan (Ma et al, 2014;Ozpolat et al, 2014;Xie et al, 2014), poly(ethylene imine) (Urban-Klein et al, 2005;Nabzdyk et al, 2014), poly(amidoamine) dendrimers (Patil et al, 2008;Conti et al, 2014) and poly(L-lysine) (Inoue et al, 2008;Kodama et al, 2014) have been extensively investigated.…”

Section: Introductionmentioning

confidence: 99%

EpCAM-targeted liposomal si-RNA delivery for treatment of epithelial cancer

et al. 2014

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Background: RNA interference (RNAi) technology using short interfering RNA (si-RNA) has shown immense potential in the treatment of cancers through silencing of specific genes. Cationic non-viral vectors employed for gene delivery exhibit toxic effects in normal cells limiting their widespread use, therefore, site-specific delivery using benign carriers could address this issue. Objective: Design of a non-toxic carrier that enables site-specific delivery of si-RNA into the cancer cells is of prime importance to realize the promise of gene silencing. Methods: In the present study, non-cationic liposomes encapsulating si-RNA against epithelial cell adhesion molecule (EpCAM) were developed and characterized for encapsulation efficiency, colloidal stability, in vitro and in vivo gene silencing efficacy. Results: PEGylated liposomes containing phosphatidyl choline and phosphatidyl ethanolamine exhibited maximum si-RNA encapsulation efficiency of 47%, zeta potential of -21 mV, phase transition temperature of 51 C and good colloidal stability in phosphate-buffered saline (PBS) containing bovine serum albumin (BSA) and plasma protein (PP) at 37 C. Conjugation of epithelial cell adhesion molecule (EpCAM) antibody to the liposomes resulted in enhanced cell internalization and superior down-regulation of EpCAM gene in MCF-7 cell lines when compared with free si-RNA and the non-targeted liposomes. In vivo evaluation of immunoliposomes for their efficacy in regressing the tumor volume in Balb/c SCID mice showed about 35% reduction of tumor volume in comparison with the positive control when administered with an extremely low dose of 0.15 mg/kg twice a week for 4 weeks. Conclusion: Our results exhibit that the nanocarrier-mediated silencing of EpCAM gene is a promising strategy to treat epithelial cancers.

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“…Intravenous injection of γPGA is mainly accumulated in the spleen and liver in mice. Kodama et al reported that a ternary complex of pDNA/dendrigraft poly-L-lysine/γPGA ( Figure 5A) displayed high transfection ef iciency only in the spleen, although pDNA/dendrigraft poly-L-lysine polyplexes induced high transfection ef iciency in the liver, lungs, and spleen [80]. Furthermore, a ternary complex of pDNA/PEI/γPGA ( Figure 5A) was taken up by a γPGA-speci ic receptor-mediated energy dependent process [81], and they showed high transgene expression in the spleen without toxicity [82,83].…”

Section: Nucleic Acidmentioning

confidence: 99%

“…Anionic polymer or its conjugate Cationic polymer or liposome Reference pDNA ᵞPGA Chitosan [66,67] pDNA ᵞPGA Dendrigraft poly-L-lysine [80] pDNA ᵞPGA PEI [81][82][83] pDNA ᵞPGA Protamine [75] pDNA αPGA DOTAP/Chol liposome [54] siRNA ᵞPGA Chitosan [73] siRNA ᵞPGA Dendrigraft poly-L-lysine [74] siRNA αPGA DOTAP/Chol liposome [77] siRNA αPGA DMAPAP/DOPE liposome [78,79] siRNA ᵞPGA PEI [76] pDNA Heparin Cationic glycopolymer (Tr4) [84] pDNA Heparin-PEI - [85] pDNA Alginic acid, Pectin Lipofectamine 2000 [24] pDNA: plasmid DNA, siRNA: small interfering RNA, ᵞPGA: poly-ᵞ-glutamic acid, αPGA: poly-α-glutamic acid, PEI: polyethylenimine, DMAPAP: 2-{3-[bis-(3-amino-propyl)-amino]-propylamino}-N-ditetradecyl carbamoyl methylacetamide, Chol: cholesterol, DOPE: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine.…”

Section: Nucleic Acidmentioning

confidence: 99%

Progress in the development of Lipoplex and Polyplex modified with Anionic Polymer for efficient Gene Delivery

Hattori¹

2017

J Genet Med Gene Ther

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Nucleic acid-based therapy has become an increasingly important strategy for treating a variety of human diseases. In systemic therapy, a therapeutic gene must be delivered effi ciently to its target tissues without side effects. To deliver a therapeutic gene such as plasmid DNA (pDNA) or small interfering RNA (siRNA) to target tissues by systemic administration, cationic carriers such as cationic liposomes and polymers have been commonly used as a non-viral vector. However, the binary complex of therapeutic gene and cationic carrier must be stabilized in the blood circulation by avoiding agglutination with blood components, because electrostatic interactions between positively charged complexes and negatively charged erythrocytes can cause agglutination, and the agglutinates contribute to high entrapment of the therapeutic genes in the highly extended lung capillaries. One promising approach for overcoming this problem is modifi cation of the surface of cationic complexes with anionic biodegradable polymers such as hyaluronic acid, chondroitin sulfate, or polyglutamic acid. As another approach, we recently developed a sequential injection method of anionic polymer and cationic liposome/therapeutic gene complex (cationic lipoplex) for delivery of a therapeutic gene into the liver or liver metastasis. In this review, we describe recent advances in the delivery of therapeutic genes by lipid-and polymerbased carrier systems using anionic polymers.

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Biodegradable nanoparticles composed of dendrigraft poly-l-lysine for gene delivery

Cited by 64 publications

References 31 publications

Heterogeneous dimer peptide-conjugated polylysine dendrimer-Fe<sub>3</sub>O<sub>4 </sub>composite as a novel nanoscale molecular probe for early diagnosis and therapy in hepatocellular carcinoma

Heterogeneous dimer peptide-conjugated polylysine dendrimer-Fe<sub>3</sub>O<sub>4 </sub>composite as a novel nanoscale molecular probe for early diagnosis and therapy in hepatocellular carcinoma

EpCAM-targeted liposomal si-RNA delivery for treatment of epithelial cancer

Progress in the development of Lipoplex and Polyplex modified with Anionic Polymer for efficient Gene Delivery

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