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- Publisher Website: 10.1021/jacs.8b12501
- Scopus: eid_2-s2.0-85061553796
- PMID: 30724083
- WOS: WOS:000459642000014
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Article: Transferrin-Appended Nanocaplet for Transcellular siRNA Delivery into Deep Tissues
Title | Transferrin-Appended Nanocaplet for Transcellular siRNA Delivery into Deep Tissues |
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Authors | |
Issue Date | 2019 |
Citation | Journal of the American Chemical Society, 2019, v. 141, n. 7, p. 2862-2866 How to Cite? |
Abstract | © 2019 American Chemical Society. Transferrin (Tf) is known to induce transcytosis, which is a consecutive endocytosis/exocytosis event. We developed a Tf-appended nanocaplet ( Tf NC⊃siRNA) for the purpose of realizing siRNA delivery into deep tissues and RNA interference (RNAi) subsequently. For obtaining Tf NC⊃siRNA, a macromonomer ( Az Gu) bearing multiple guanidinium (Gu + ) ion units, azide (N 3 ) groups, and trityl (Trt)-protected thiol groups in the main chain, side chains, and termini, respectively, was newly designed. Because of a multivalent Gu + -phosphate salt-bridge interaction, Az Gu can adhere to siRNA along its strand. When I 2 was added to a preincubated mixture of Az Gu and siRNA, oxidative polymerization of Az Gu took place along the siRNA strand, affording Az NC⊃siRNA, the smallest siRNA-containing reactive nanocaplet so far reported. This conjugate was converted into Glue/BP NC⊃siRNA by the click reaction with a Gu + -appended bioadhesive dendron (Glue) followed by a benzophenone derivative (BP). Then, Tf was covalently immobilized onto Glue/BP NC⊃siRNA by Gu + -mediated adhesion followed by photochemical reaction with BP. With the help of Tf-induced transcytosis, Tf NC⊃siRNA permeated deeply into a cancer spheroid, a 3D tissue model, at a depth of up to nearly 70 μm, unprecedentedly. |
Persistent Identifier | http://hdl.handle.net/10722/276631 |
ISSN | 2023 Impact Factor: 14.4 2023 SCImago Journal Rankings: 5.489 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Kohata, Ai | - |
dc.contributor.author | Hashim, P. K. | - |
dc.contributor.author | Okuro, Kou | - |
dc.contributor.author | Aida, Takuzo | - |
dc.date.accessioned | 2019-09-18T08:34:11Z | - |
dc.date.available | 2019-09-18T08:34:11Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Journal of the American Chemical Society, 2019, v. 141, n. 7, p. 2862-2866 | - |
dc.identifier.issn | 0002-7863 | - |
dc.identifier.uri | http://hdl.handle.net/10722/276631 | - |
dc.description.abstract | © 2019 American Chemical Society. Transferrin (Tf) is known to induce transcytosis, which is a consecutive endocytosis/exocytosis event. We developed a Tf-appended nanocaplet ( Tf NC⊃siRNA) for the purpose of realizing siRNA delivery into deep tissues and RNA interference (RNAi) subsequently. For obtaining Tf NC⊃siRNA, a macromonomer ( Az Gu) bearing multiple guanidinium (Gu + ) ion units, azide (N 3 ) groups, and trityl (Trt)-protected thiol groups in the main chain, side chains, and termini, respectively, was newly designed. Because of a multivalent Gu + -phosphate salt-bridge interaction, Az Gu can adhere to siRNA along its strand. When I 2 was added to a preincubated mixture of Az Gu and siRNA, oxidative polymerization of Az Gu took place along the siRNA strand, affording Az NC⊃siRNA, the smallest siRNA-containing reactive nanocaplet so far reported. This conjugate was converted into Glue/BP NC⊃siRNA by the click reaction with a Gu + -appended bioadhesive dendron (Glue) followed by a benzophenone derivative (BP). Then, Tf was covalently immobilized onto Glue/BP NC⊃siRNA by Gu + -mediated adhesion followed by photochemical reaction with BP. With the help of Tf-induced transcytosis, Tf NC⊃siRNA permeated deeply into a cancer spheroid, a 3D tissue model, at a depth of up to nearly 70 μm, unprecedentedly. | - |
dc.language | eng | - |
dc.relation.ispartof | Journal of the American Chemical Society | - |
dc.title | Transferrin-Appended Nanocaplet for Transcellular siRNA Delivery into Deep Tissues | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1021/jacs.8b12501 | - |
dc.identifier.pmid | 30724083 | - |
dc.identifier.scopus | eid_2-s2.0-85061553796 | - |
dc.identifier.volume | 141 | - |
dc.identifier.issue | 7 | - |
dc.identifier.spage | 2862 | - |
dc.identifier.epage | 2866 | - |
dc.identifier.eissn | 1520-5126 | - |
dc.identifier.isi | WOS:000459642000014 | - |
dc.identifier.issnl | 0002-7863 | - |