Enhancement of gene transfer activity mediated by mannosylated dendrimer/α-cyclodextrin conjugate (generation 3, G3)

Arima, Hisatomi; Chihara, Yuko; Arizono, Masayo; Yamashita, Shogo; Wada, Koh; Hirayama, Fumitoshi; Uekama, Kaneto

doi:10.1016/j.jconrel.2006.08.026

Cited by 75 publications

(66 citation statements)

References 38 publications

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“…All the CD-grafted cationic polymers showed reduced cytotoxicity by grafting the CD moieties. Uekama et al [111][112][113][114][115][116] systematically studied CD-grafting PAMAM dendrimers with different generations (G2, G3, and G4) and attributed the enhancing gene transfection effect to increasing cellular association and intracellular trafficking of plasmid DNA.…”

Section: Cyclodextrin-containing Cationic Polymers For Gene Deliverymentioning

confidence: 99%

Supramolecular Polymers Based on Cyclodextrins for Drug and Gene Delivery

Zhao

2010

Biofunctionalization of Polymers and Their Applications

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Supramolecular polymers based on cyclodextrins (CDs) have inspired interesting and rapid developments as novel biomaterials in a broad range of drug and gene delivery applications, due to their low cytotoxicity, controllable size, and unique architecture. This review will summarize the potential applications of polyrotaxanes in the field of drug delivery and gene delivery. Generally, cyclodextrin-based biodegradable polypseudorotaxane hydrogels could be used as a promising injectable drug delivery system for sustained and controlled drug release. Temperature-responsive, pH-sensitive, and controllable hydrolyzable polyrotaxane hydrogels have attracted much attention because of their controllable properties, and the self-assembly micelles formed by amphiphilic copolymer threaded with CDs could be used as a carrier for controlled and sustained drug release. Polyrotaxanes with drug or ligand conjugated CDs threaded on a polymer chain with a biodegradable end group could be useful for controlled and multivalent targeted delivery. In the field of gene delivery, cationic polyrotaxanes consisting of multiple OEI-grafted CDs threaded on a block copolymer chain are attractive non-viral gene carries due to the strong DNA-binding ability, low cytotoxicity, and high gene delivery capability. Furthermore, cytocleavable end-caps were introduced in the polyrotaxane systems in order to ensure efficient endosomal escape for intracellular trafficking of DNA. The development of the supramolecular approach using CD-containing polyrotaxanes is expected to provide a new paradigm for biomaterials.

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Section: Cyclodextrin-containing Cationic Polymers For Gene Deliverymentioning

confidence: 99%

Supramolecular Polymers Based on Cyclodextrins for Drug and Gene Delivery

Zhao

2010

Biofunctionalization of Polymers and Their Applications

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“…Thus, glycosylation of polymers is an effective method to deliver gene to target cells and/or to enhance gene transfer activity. To possess the cell-specific gene transfer activity of α-CDE (G3, DS2), we prepared the three types of sugar-appended α-CDEs: mannosylated α-CDEs [Man-α-CDEs (G2, G3)] [67,81], galactosylated α-CDEs [Gal-α-CDEs (G2)] [82] and lactosylated α-CDEs [Lac-α-CDE (G2)] [75] with the various degree of substitution (DS) of these sugar moieties (Figure 4). …”

Section: Sugar-appended α-Cdes As Dna Carriersmentioning

confidence: 99%

“…Secondly, to improve APC-specific gene transfer activity of Man-α-CDE (G2), we prepared Man-α-CDEs (G3) with various DSM (5, 10, 13, 20) and compared their cytotoxicity and gene transfer activity, and elucidated the enhancing mechanism for the activity [81]. Of the various carriers used here, Man-α-CDE (G3, DSM10) provided the highest gene transfer activity in NR8383, A549, NIH3T3 and HepG2 cells and the activity of Man-α-CDE (G3, DSM10) was not decreased by the addition of 10% serum in A549 cells.…”

Section: Sugar-appended α-Cdes As Dna Carriersmentioning

confidence: 99%

Recent Findings Concerning PAMAM Dendrimer Conjugates with Cyclodextrins as Carriers of DNA and RNA

Arima

Motoyama

2009

Sensors

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We have evaluated the potential use of various polyamidoamine (PAMAM) dendrimer [dendrimer, generation (G) 2-4] conjugates with cyclodextrins (CyDs) as novel DNA and RNA carriers. Among the various dendrimer conjugates with CyDs, the dendrimer (G3) conjugate with α-CyD having an average degree of substitution (DS) of 2.4 [α-CDE (G3, DS2)] displayed remarkable properties as DNA, shRNA and siRNA delivery carriers through the sensor function of α-CDEs toward nucleic acid drugs, cell surface and endosomal membranes. In an attempt to develop cell-specific gene transfer carriers, we prepared sugar-appended α-CDEs. Of the various sugar-appended α-CDEs prepared, galactose- or mannose-appended α-CDEs provided superior gene transfer activity to α-CDE in various cells, but not cell-specific gene delivery ability. However, lactose-appended α-CDE [Lac-α-CDE (G2)] was found to possess asialoglycoprotein receptor (AgpR)-mediated hepatocyte-selective gene transfer activity, both in vitro and in vivo. Most recently, we prepared folate-poly(ethylene glycol)-appended α-CDE [Fol-PαC (G3)] and revealed that Fol-PαC (G3) imparted folate receptor (FR)-mediated cancer cell-selective gene transfer activity. Consequently, α-CDEs bearing integrated, multifunctional molecules may possess the potential to be novel carriers for DNA, shRNA and siRNA.

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“…To date, mannose modified non-viral vectors, including cationic liposomes, 4,5) polyethyleneimine, 6,7) dendrimers, 8) and chitosan 9,10) have been reported to achieve targeted gene delivery into APCs via mannose receptor-mediated endocytosis.…”

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confidence: 99%

“…2,3) It is known that the mannose receptor is a 175 kDa protein expressed on the surface of APCs and it recognizes the terminal of mannose groups. To date, mannose modified non-viral vectors, including cationic liposomes, 4,5) polyethyleneimine, 6,7) dendrimers, 8) and chitosan 9,10) have been reported to achieve targeted gene delivery into APCs via mannose receptor-mediated endocytosis.…”

mentioning

confidence: 99%

Enhanced Gene Transfection in Macrophages by Histidine-Conjugated Mannosylated Cationic Liposomes

Nakamura

Kuramoto

Mukai

et al. 2009

Biological & Pharmaceutical Bulletin

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The use of non-viral carriers has attracted great interest for in vivo gene delivery since they are free from some of the risks inherent in these systems compared with viral vectors. Furthermore, non-viral carriers are easier to prepare and to modify by chemical approaches. To achieve cell-selective targeted in vivo gene transfection, a number of receptor-mediated non-viral carriers have been developed. 1) Antigen presenting cells (APCs) such as macrophages and dendritic cells are important targets for DNA vaccine therapy.2,3) It is known that the mannose receptor is a 175 kDa protein expressed on the surface of APCs and it recognizes the terminal of mannose groups. To date, mannose modified non-viral vectors, including cationic liposomes, 4,5) polyethyleneimine, 6,7) dendrimers, 8) and chitosan 9,10) have been reported to achieve targeted gene delivery into APCs via mannose receptor-mediated endocytosis.Recently, we reported that mannosylated cationic liposomes modified with cholesten-5-yloxy-N-(4-((1-imino-2-Dthiomannosylethyl)amino)butyl)formamide (Man-C4-Chol) enhanced DNA vaccine potency through efficiently targeted gene delivery to APCs in mice. 11,12) However, the degradation of plasmid DNA in the lysosomes after their incorporation into cells is a rate-limiting step for transfection in macrophages. 13,14) Therefore, an escape path from the endosomes needs to be introduced into our mannosylated cationic liposomes for more efficient gene transfer in macrophages. Histidine is known to have pH-buffering capacity under the slightly acidic conditions such as are found in lysosomes and, accordingly, it could enhance the cytoplasmic distribution of plasmid DNA before degradation in lysosomes.15) More recently, we have demonstrated that histidine-conjugated galactosylated liposomes, which possess pH-buffering capacity, can provide efficient hepatocyte-selective gene transfer in human hepatoma HepG2 cells. 16) In this study, we extended our earlier investigations 5,16) and a pH-sensitive mannosylated cholesterol derivative, ManHis-C4-Chol (Chart 1), which possesses histidine residues, containing lipoplexes (Man-His-lipoplexes) was characterized for transfection both in vitro and in vivo. Man-Hislipoplexes possess multi-functional properties for efficient transfection into macrophages, i.e., i) cholesterol for their stable incorporation into cationic liposomes, ii) a mannose group for recognition by mannose receptors in macrophages, iii) an imino group for binding plasmid DNA without loss of the cationic nature of the cationic liposomes, iv) a histidine group to allow an endosomal escape by the pH-buffering capacity. Since the physicochemical properties of mannosylated lipoplexes are also important to achieve cell-selective gene transfection, 1) the His group was directly introduced into our previously synthesized mannosylated cholesterol derivative, Man-C4-Chol; consequently, a pH-buffering capacity could be introduced in the formulation without any significant change into the optimal physicochemical properties.Fi...

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Enhancement of gene transfer activity mediated by mannosylated dendrimer/α-cyclodextrin conjugate (generation 3, G3)

Cited by 75 publications

References 38 publications

Supramolecular Polymers Based on Cyclodextrins for Drug and Gene Delivery

Supramolecular Polymers Based on Cyclodextrins for Drug and Gene Delivery

Recent Findings Concerning PAMAM Dendrimer Conjugates with Cyclodextrins as Carriers of DNA and RNA

Enhanced Gene Transfection in Macrophages by Histidine-Conjugated Mannosylated Cationic Liposomes

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