Photodimerization and Polymerization of PEG Derivatives through Radical Coupling using Photochemistry of Dithiocarbamate

Nakayama, Yasuhide; Ishikawa, Ayaka; Sato, Ryo; Uchida, Kôji; Kambe, Nobuaki

doi:10.1295/polymj.pj2008132

Cited by 5 publications

(4 citation statements)

References 23 publications

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“…Therefore, benzyl radicals are selectively consumed by UV irradiation to generate bibenzyl. As expected, a dimer was produced from a PEG derivative with dithiocarbamate at one terminus, and a polymer was produced from the PEG derivative with dithiocarbamate at both termini . This study indicated that the terminal ends of the dithiocarbamate-derivatized polymers could be cross-linked by photoirradiation alone, without using a chemical cross-linking agent such as glutaraldehyde or diisocyanate.…”

Section: Approach 3: Intermolecular Cross-linkingsupporting

confidence: 66%

“…As expected, a dimer was produced from a PEG derivative with dithiocarbamate at one terminus, and a polymer was produced from the PEG derivative with dithiocarbamate at both termini. 31 This study indicated that the terminal ends of the dithiocarbamate-derivatized polymers could be cross-linked by photoirradiation alone, without using a chemical cross-linking agent such as glutaraldehyde or diisocyanate. The cross-linking may be applied to molecular architecture to prepare more complex-shaped polymers, such as mesh or hyper-branch structures.…”

Section: Approach 3: Intermolecular Cross-linkingmentioning

confidence: 88%

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Hyperbranched Polymeric “Star Vectors” for Effective DNA or siRNA Delivery

Nakayama

2012

Acc. Chem. Res.

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Although gene therapy offers an attractive strategy for treating inherited disorders, current techniques using viral and nonviral delivery systems have not yielded many successful results in clinical trials. Viral vectors such as retroviruses, lentiviruses, and adenoviruses deliver genes efficiently; however, the possibility of negative outcomes from viral transformation cannot be completely ruled out. In contrast, various types of nonviral vectors are attracting considerable attention because they are easier to handle and induce weak immune responses. Cationic polymers, such as polyethylenimine (PEI) and poly(N,N-dimethylaminopropyl acrylamide) (PDMAPAAm), can generate nanoparticles through the formation of polyion complexes, "polyplexes" with DNA. These nonviral systems offer many advantages over viral systems. The primary obstacle to implementing these cationic polymers in an effective gene therapy remains their comparatively inefficient gene transfection in vivo. We describe four strategies for the development of hyperbranched star vectors (SVs) for enhancing DNA or siRNA delivery. The molecular design was performed by living radical polymerization in which the chain length can be controlled by photoirradiation and solution conditions, including concentrations of the monomer or iniferter (a molecule that serves as a combination of initiator, transfer agent, and terminator). The branch composition is controlled by the types of monomers that are added stepwise. In our first strategy, we prepared a series of only cationic PDMAPAAm-based SVs with no branches or 3, 4, or 6 branching numbers. These SVs could form polyion complexes (polyplexes) by mixing with DNA only in aqueous solution. The relative gene expression activity of the delivered DNA increased according to the degree of branching. In addition, increasing the molecular weight of SVs and narrowing their polydispersity index (PDI) improved their activity. For targeting DNA delivery to the specific cells, we modified the SV with ligands. Interestingly, the SV could adsorb the RGD peptide, making gene transfer possible in endothelial cells which are usually refractory to such treatments. The peptide was added to the polyplex solution without covalent derivatization to the SV. The introduction of additional branching by cross-linking using iniferter-induced coupling reactions further improved gene transfection activity. After block copolymerization of PDMAPAAm-based SVs with a nonionic monomer (DMAAm), the blocked SVs (BSVs) produced polyplexes with DNA that had excellent colloidal stability for 1 month, leading to efficient in vitro and in vivo gene delivery. Moreover, BSVs served as carriers for siRNA delivery. BSVs enhanced siRNA-mediated gene silencing in mouse liver and lung. As an alternative approach, we developed a novel gene transfection method in which the polyplexes were kept in contact with their deposition surface by thermoresponsive blocking of the SV. This strategy was more effective than reverse transfection and the conventional transfection m...

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Section: Approach 3: Intermolecular Cross-linkingsupporting

confidence: 66%

Section: Approach 3: Intermolecular Cross-linkingmentioning

confidence: 88%

Hyperbranched Polymeric “Star Vectors” for Effective DNA or siRNA Delivery

Nakayama

2012

Acc. Chem. Res.

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“…As expected, chain transfer of polymer radicals to the polymer matrix also produced CSV in another cross-linking manner, in which the end chains of the SV branch bonded to the side chain of another SV branch. Photoinduced cross-linking with DC groups has previously been performed for the surface modification of medical materials for better biocompatibility (32) or polymer design (33).…”

Section: Resultsmentioning

confidence: 99%

Photoinduced Cross-Linking of Star Vector for Improvement of Gene Transfer Efficiency

et al. 2008

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This study aimed to investigate the effect of cross-linking of a cationic nonviral gene carrier on gene expression. As a precursor for photo-cross-linking, a star-shaped, six-branched cationic polymer of poly(N,N-dimethylaminopropylacrylamide) (six-branched star vector, SV), which was previously designed as a gene carrier, was synthesized by iniferter-based living radical polymerization. Upon UV irradiation, the number-average molecular weight (Mn) of the SV increased from ca. 28 kDa to ca. 32 kDa (irradiation time, 180 min) and ca. 46 kDa (240 min) with broadness of the polydispersity due to the coupling reaction between the polymer radicals generated at the terminal ends of each branch of the SVs, resulting in the preparation of cross-linked SVs (CSVs) without the use of any chemical cross-linking agents. Irrespective of cross-linking, all the SVs were able to interact with and condense luciferase-encoding plasmid DNA to yield relatively stable polymer/DNA complexes (polyplexes) of approximate diameter 150 nm with zeta-potential of ca. 20 mV. However, a transfection study using several types of cell lines, HeLa, Hep G2, 293, and COS-1, showed that by cross-linking of SVs the luciferase activity increased drastically. The activity with CSV (Mn=ca. 46 kDa) was increased by at least 1 order of magnitude in the original SV (Mn=ca. 28 kDa), which was several-fold that in the SV with the same molecular weight in all cells. In all SVs, no significant cellular cytotoxicity was observed even at a high charge ratio of 45. The SV-based gene transfection was significantly enhanced by the cross-linking of the SVs.

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“…5,6 Each isomer has a specific application in the polymer industry and synthetic field. [7][8][9] For instance, trans-1,2-dichloroethene (trans-DCE) is used in the extraction of rubber and as a refrigerant, while cis-1, 2-dichloroethene (cis-DCE) is a foam-blowing additive. 10,11 Thus, obtaining the pure cis-and trans-DCE isomers is of great industrial and economic importance.…”

mentioning

confidence: 99%