Chondroitin Sulfate as a Molecular Portal That Preferentially Mediates the Apoptotic Killing of Tumor Cells by Penetratin-directed Mitochondria-disrupting Peptides

Yang, Hao; Liu, Shan; Cai, Huawei; Wan, Lin; Li, Shengfu; Liu, You‐Ping; Cheng, Jun; Lu, Xiaofeng

doi:10.1074/jbc.m109.089417

Cited by 38 publications

(32 citation statements)

References 39 publications

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“…7,8 Antp has seven positively charged residues at physiological pH and has been shown to bind membranes composed of negatively charged lipids and to bind GAGs. [8][9][10] Using circular dichroism it was found that the Antp peptide undergoes a conformational transition from random coil to a b-sheet upon binding to negatively charged DOPG lipids.…”

Section: Introductionmentioning

confidence: 99%

“…10,14,[16][17][18][19][20] Experiments have shown the reduced internalization efficiency of CPPs following the addition of exogenous heparin, in cells not expressing cell surface GAGs and in cells treated with heparinase enzymes. 9,10,17,18,[21][22][23][24] The translocation of Antp and TAT has been observed to be mediated by specific interactions with the heparan sulfate chains of syndecan-4, belonging to the syndecan family of transmembrane proteoglycans. 16 However, in addition to these findings, experimental evidence has also been reported that indicates, in the case of TAT, that uptake into the cell can occur even in the absence of cell surface GAGs.…”

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confidence: 98%

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Peptide–glycosaminoglycan cluster formation involving cell penetrating peptides

2011

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Glycosaminoglycans (GAGs) affect the efficiency of cellular uptake of a wide range of cell penetrating peptides (CPPs). GAGs have been proposed to cluster with CPPs at the cell surface before uptake but little is known about the formation or stability of CPP-GAG clusters. Here we apply a combination of heparin affinity chromatography, dynamic light scattering, and fluorescence spectroscopy to characterize the formation, stability, and size of the clusters formed between CPPs and heparin. Under conditions similar to those used in cell uptake experiments the CPP, penetratin (Antp), was observed to form significantly more stable clusters with heparin than the CPP TAT, despite TAT showing a comparable affinity for heparin. This difference in cluster stability may explain the origins of the preferred cell uptake pathways followed by Antp and TAT, and may be an important parameter for optimizing the efficiency of designed CPP delivery vectors.

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Peptide–glycosaminoglycan cluster formation involving cell penetrating peptides

2011

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“…CS did not exhibit the same anticoagulant properties as FC, but there are some reports in the literature showing antinflamatory 49 and anticancer activities. 50,51 For these reasons, these CS NPs can be tested as a new anticancer system with carrier properties. In this work, NP1 was prepared only as a nanocoacervation model for NP2, for economic reasons.…”

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Preparation and characterization of polysaccharide-based nanoparticles with anticoagulant activity

Silva¹,

Garcia²,

Mori³

et al. 2012

IJN

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Abstract:The aim of this study was to produce and characterize nanoparticles (NPs), combining chondroitin sulfate (CS) and fucoidan (FC) with chitosan for therapeutic purposes. These NPs were characterized by dynamic light scattering, zeta potential determination, and transmission electronic microscopy. The anticoagulant activity was determined for FC NPs and compared with FC solution at the same concentration. FC NPs showed regular shapes and better anticoagulant activity than free polysaccharide solution. FC solution did not affect coagulation compared to FC NPs, which increased up to two-fold, even at a lower concentration. Cytotoxicity and permeability tests were conducted using Caco-2 cell monolayer, exhibiting no toxic effect in this cell line and higher permeability for NP2 samples than FC solution at the same concentration.

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“…[21][22][23][24][25] Moreover, some reports have shown that CS has anti-inflammatory activities and anticancer activities. [26][27][28] …”

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Ternary Complex of Plasmid DNA Electrostatically Assembled with Polyamidoamine Dendrimer and Chondroitin Sulfate for Effective and Secure Gene Delivery

Imamura

Kodama

Higuchi

et al. 2014

Biological & Pharmaceutical Bulletin

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The purpose of this study was to develop a ternary complex of plasmid DNA (pDNA) electrostatically assembled with polyamidoamine (PAMAM) dendrimer and chondroitin sulfate (CS) for effective and secure gene delivery. PAMAM dendrimers are new cationic polymers that are expected to be used as gene delivery vectors. However, cationic non-viral gene vectors showed cytotoxicity by binding to negative cellular membranes. We therefore prepared a ternary complex by adding CS, an anionic polymer, and examined its usefulness. The pDNA/PAMAM dendrimer complex (PAMAM dendriplex) and the PAMAM dendriplex coated by CS (CS complex) showed nanoparticles with positive ζ-potential and negative ζ-potential, respectively. The CS complex had no cytotoxicity against B16-F10 cells and no agglutination activity, although severe cytotoxicity and high agglutination were observed in the PAMAM dendriplex. As a result of an in vitro gene expression study of B16-F10 cells, not only the PAMAM dendriplex but also the CS complex showed high transfection efficiency. The transfection efficiency of the CS complex was significantly inhibited by clathrinmediated endocytosis inhibitor (chlorpromazine), caveolae-mediated endocytosis inhibitor (genistein), and hypothermia. Tail-vein injection of the CS complex into mice led to significantly higher gene expression in the spleen than the PAMAM dendriplex. Thus, the ternary complex of pDNA electrostatically assembled with PAMAM denriplex and CS showed safe high gene expression in the spleen. This vector is expected to be useful for useful gene delivery.Key words ternary complex; chondroitin sulfate; polyamidoamine dendrimer; gene delivery Gene therapy is expected to be an effective method to treat cancer, infection, innate immunodeficiency and cardiovascular diseases.1-4) The success of gene therapy is largely dependent on the development of vectors capable of effectively delivering foreign genes into targeted cells. One major approach in gene therapy is based on cationic polymers, such as polyethylenimine (PEI), polylysine, polyarginine, and chitosan.5-8) When cationic polymer-encapsulated plasmid DNA (pDNA) makes association with the cell surface, it enters the cells by endocytosis.Polyamidoamine (PAMAM) dendrimers are new cationic polymers, which are highly branched radial polymers that have specific and systematically variable size, shape and chemical structure. Their radical structure contains a 2-carbon ethylenediamine core and primary amino groups on the surface. Successive generations (G) have increasing diameter and double the surface functional amino groups of the preceding generation.9,10) PAMAM dendrimers can be used as carriers for pDNA and show high transfection efficiency. 11,12)The pDNA/PAMAM dendrimer complexes (PAMAM dendriplex) are formed by electrostatic interactions and initiate cell entry through binding to anionic phospholipids on the cell membrane. With increasing generations of dendrimers, the PAMAM dendriplex showed higher transfection efficiency, which depended on the charge rati...

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Chondroitin Sulfate as a Molecular Portal That Preferentially Mediates the Apoptotic Killing of Tumor Cells by Penetratin-directed Mitochondria-disrupting Peptides

Cited by 38 publications

References 39 publications

Peptide–glycosaminoglycan cluster formation involving cell penetrating peptides

Peptide–glycosaminoglycan cluster formation involving cell penetrating peptides

Preparation and characterization of polysaccharide-based nanoparticles with anticoagulant activity

Ternary Complex of Plasmid DNA Electrostatically Assembled with Polyamidoamine Dendrimer and Chondroitin Sulfate for Effective and Secure Gene Delivery

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