Light-induced gene transfer from packaged DNA enveloped in a dendrimeric photosensitizer

Nishiyama, Nobuhiro; Iriyama, Aya; Jang, Woo Dong; Miyata, Kanjiro; Itaka, Keiji; Inoue, Yoshito; Takahashi, Hidenori; Yanagi, Yasuo; Tamaki, Yasuhiro; Koyama, Hiroyuki; Kataoka, Kazunori

doi:10.1038/nmat1524

Cited by 326 publications

(239 citation statements)

References 27 publications

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“…Moreover, this strategy enables longer RNAi effects to be obtained with one single dose of siRNA nanocarrier, thereby avoiding the need for a second administration to obtain the same effect longevity. The incorporation of the photosensitizing agent into the nanocarrier itself could be a valuable addition to this concept [34]. The siRNA impregnated nanogels are scheduled to be tested in vivo following local injection in combination with PCI at different time-points following administration.…”

Section: Resultsmentioning

confidence: 99%

Prolonged gene silencing by combining siRNA nanogels and photochemical internalization

Raemdonck

Naeye

Høgset

et al. 2010

Journal of Controlled Release

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Small interfering RNAs (siRNAs) show potential for the treatment of a wide variety of pathologies with a known genetic origin through sequence-specific gene silencing. However, siRNAs do not have favorable drug-like properties and need to be packaged into nanoscopic carriers that are designed to guide the siRNA to the cytoplasm of the target cell. In this report biodegradable cationic dextran nanogels are used to deliver siRNA across the intracellular barriers. For the majority of non-viral siRNA carriers studied so far, endosomal confinement is identified as the most prominent hurdle, limiting the full gene silencing potential. Thus, there is a major interest in methods that are able to enhance endosomal escape of siRNA to improve its intracellular bioavailability. Photochemical internalization (PCI) is a method that employs amphiphilic photosensitizers to destabilize endosomal vesicles. We show that applying PCI at a later time-point post-transfection significantly prolonged the knockdown of the target protein only in case the siRNA was carried by nanogels and not when a liposomal carrier was used. Combining siRNA nanogels and PCI creates new possibilities to prolong gene silencing by using intracellular vesicles as depots for siRNA and applying PCI at the time when maintaining the RNAi effect becomes critical. Graphical abstractCombining siRNA nanogels and photochemical internalization (PCI) creates new possibilities to prolong gene silencing by using intracellular vesicles as depots and applying PCI at the time when maintaining the RNAi effect becomes critical.

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Section: Resultsmentioning

confidence: 99%

Prolonged gene silencing by combining siRNA nanogels and photochemical internalization

Raemdonck

Naeye

Høgset

et al. 2010

Journal of Controlled Release

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“…[1][2][3][4][5][6][7][8][9][10][11][12] A gene-transferring system mediated by a particulate DNA-calcium phosphate composite [1][2][3] is safer than viral [4][5][6] and lipid-based [7][8][9] systems, but its transferring efficiency is comparatively low. To enhance the gene-transferring efficiency, a surface-mediated genetransferring system derived from a DNA-apatite composite (D-Ap) layer has been developed.…”

mentioning

confidence: 99%

Novel gene-transferring scaffolds having a cell adhesion molecule–DNA–apatite nanocomposite surface

2007

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A low efficiency has long been the most critical problem of conventional gene-transferring systems using calcium phosphates, and this was successfully improved on by using a laminin-DNA-apatite composite (LD-Ap) layer. The genetransferring efficiency of the LD-Ap surface was 1-2 orders of magnitude higher than that of a DNA-calcium phosphate composite surface. This is because laminin enhances cell adhesion and spreading, and this provides regions of high DNA concentration between a cell and the LD-Ap surface. The efficiency of gene transfer of the LD-Ap surface was equivalent to, or even higher than that mediated using a commercial lipid-based transfection reagent applied using the manufacture's recommended optimum conditions. In addition, the gene-transferring efficiency of our system could be controlled by changing the laminin and DNA content in the LD-Ap layer. Moreover, our system is composed of highly safe reagents: apatite, DNA and laminin, all of which are present in the human body. Hence, the LD-Ap surface, which enhances cell attachment on its surface, and mediates a safe, highly efficient and controllable gene transfer, is highly applicable to tissue engineering and gene therapy applications. Gene Therapy (2007) An efficient and safe gene-transferring system is a key technology in tissue engineering and gene therapy applications. 1-12 A gene-transferring system mediated by a particulate DNA-calcium phosphate composite 1-3 is safer than viral 4-6 and lipid-based 7-9 systems, but its transferring efficiency is comparatively low. To enhance the gene-transferring efficiency, a surface-mediated genetransferring system derived from a DNA-apatite composite (D-Ap) layer has been developed. 12 In this system, regions of high DNA concentration are produced locally around cells, and this enhances the gene-transferring efficiency. In this work, the cell adhesion molecule, laminin, 13,14 was immobilized on a D-Ap layer to enhance further the gene-transferring efficiency by strengthening a cell's attachment and facilitating its spreading on a coating's surface. The gene-transferring efficiency was 1-2 orders of magnitude higher on the resulting laminin-DNA-apatite composite (LD-Ap) layer than the gene-transferring efficiency on a D-Ap layer. In this paper, we present an advanced gene-transferring system that has a high efficiency, is safe and has a great potential for use in tissue engineering and gene therapy applications.An LD-Ap layer was coated on a polymer surface in a metastable supersaturated calcium phosphate solution at neutral pH, and ambient pressure and temperature. [15][16][17][18] As controls, an apatite (Ap) layer, a D-Ap layer and a laminin-apatite composite (L-Ap) layer were also coated on the polymer surface. The coating layers were formed by immersing the polymer sample, that had an amorphous calcium phosphate (ACP) layer deposited on its surface, in four different coating solutions: a calcium phosphate solution (CP solution) [15][16][17][18] (for the Ap layer), a CP solution supplemented with DN...

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“…52 The ternary complex was prepared by simply adding DPc to the cationic pDNA-CP4 complex, which was obtained by mixing pDNA …”

Section: Ternary Complex System For Gene Deliverymentioning

confidence: 99%

“…Adding DPc to the cationic pDNA-CP4 complex creates a ternary complex 130 nm in diameter with a narrow size distribution. 52 In contrast, linear poly(aspartic acid) (degree of polymerization ¼ 26) does not form spherical nanoparticles when added to pDNA-CP4 complexes, suggesting that the three-dimensional structure of DPc plays an essential role in forming the ternary complex. The ternary complex enhanced in vitro transgene expression more than 100-fold following light irradiation, without severe photocytotoxicity.…”

Section: Dp-based Self-assembled Nano Devices Y-h Jeong Et Almentioning

confidence: 99%

Dendrimer porphyrin-based self-assembled nano-devices for biomedical applications

Jeong

Yoon

Jang

2012

Polym J

Self Cite

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Dendrimers have attracted great interest for the design of functional materials. Because the core porphyrin unit in dendrimer porphyrin (DP) is surrounded by large poly(benzyl ether) dendritic wedges with ionic peripheries, the resulting electrostatic interaction with oppositely charged polymeric materials has been used to create various functional nano-devices. In this paper, we briefly review DP-based self-assembled biomedical nano-devices, including DP-loaded polyion complex micelles, the ternary complex systems used for gene delivery, polymer-metal complex micelles, the hollow nanocapsules used for combination cancer therapy, and the DP-immobilized surfaces used for diagnostic tools.

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Light-induced gene transfer from packaged DNA enveloped in a dendrimeric photosensitizer

Cited by 326 publications

References 27 publications

Prolonged gene silencing by combining siRNA nanogels and photochemical internalization

Prolonged gene silencing by combining siRNA nanogels and photochemical internalization

Novel gene-transferring scaffolds having a cell adhesion molecule–DNA–apatite nanocomposite surface

Dendrimer porphyrin-based self-assembled nano-devices for biomedical applications

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