File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Optimization of PEGylated KL4 Peptide for siRNA Delivery with Improved Pulmonary Tolerance

TitleOptimization of PEGylated KL4 Peptide for siRNA Delivery with Improved Pulmonary Tolerance
Authors
Keywordslung surfactant
monodisperse PEG
PEGylation
peptide
pulmonary delivery
Issue Date2021
PublisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/mpohbp/index.html
Citation
Molecular Pharmaceutics, 2021, v. 18 n. 6, p. 2218-2232 How to Cite?
AbstractPulmonary delivery of small interfering RNA (siRNA) is a promising therapeutic strategy for treating various respiratory diseases but an effective carrier for the delivery of siRNA into the cells of the lungs and a robust gene-silencing effect is still lacking. Previously, we reported that the KL4 peptide, a synthetic cationic peptide with a repeating KLLLL sequence, can mediate effective siRNA transfection in lung epithelial cells but its high hydrophobic leucine content, and hence poor water solubility, limits its application as a delivery vector. Here, we show that the covalent attachment of monodisperse poly(ethylene glycol) (PEG) improves the solubility of KL4 and the uptake of its complex with siRNA into lung epithelial cells, such that very robust silencing is produced. All PEGylated KL4 peptides, with PEG length varying between 6 and 24 monomers, could bind and form nanosized complexes with siRNA, but the interaction between siRNA and peptides became weaker as the PEG chain length increased. All PEGylated KL4 peptides exhibited satisfactory siRNA transfection efficiency on three human lung epithelial cell lines, including A549 cells, Calu-3 cells, and BEAS-2B cells. The PEG12KL4 peptide, which contains 12 monomers of PEG, was optimal for siRNA delivery and also demonstrated a low risk of inflammatory response and toxicity in vivo following pulmonary administration.
Persistent Identifierhttp://hdl.handle.net/10722/300697
ISSN
2023 Impact Factor: 4.5
2023 SCImago Journal Rankings: 0.940
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorQiu, Y-
dc.contributor.authorClarke, M-
dc.contributor.authorWan, TLL-
dc.contributor.authorLo, JCK-
dc.contributor.authorMason, AJ-
dc.contributor.authorLam, JKW-
dc.date.accessioned2021-06-18T14:55:45Z-
dc.date.available2021-06-18T14:55:45Z-
dc.date.issued2021-
dc.identifier.citationMolecular Pharmaceutics, 2021, v. 18 n. 6, p. 2218-2232-
dc.identifier.issn1543-8384-
dc.identifier.urihttp://hdl.handle.net/10722/300697-
dc.description.abstractPulmonary delivery of small interfering RNA (siRNA) is a promising therapeutic strategy for treating various respiratory diseases but an effective carrier for the delivery of siRNA into the cells of the lungs and a robust gene-silencing effect is still lacking. Previously, we reported that the KL4 peptide, a synthetic cationic peptide with a repeating KLLLL sequence, can mediate effective siRNA transfection in lung epithelial cells but its high hydrophobic leucine content, and hence poor water solubility, limits its application as a delivery vector. Here, we show that the covalent attachment of monodisperse poly(ethylene glycol) (PEG) improves the solubility of KL4 and the uptake of its complex with siRNA into lung epithelial cells, such that very robust silencing is produced. All PEGylated KL4 peptides, with PEG length varying between 6 and 24 monomers, could bind and form nanosized complexes with siRNA, but the interaction between siRNA and peptides became weaker as the PEG chain length increased. All PEGylated KL4 peptides exhibited satisfactory siRNA transfection efficiency on three human lung epithelial cell lines, including A549 cells, Calu-3 cells, and BEAS-2B cells. The PEG12KL4 peptide, which contains 12 monomers of PEG, was optimal for siRNA delivery and also demonstrated a low risk of inflammatory response and toxicity in vivo following pulmonary administration.-
dc.languageeng-
dc.publisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/mpohbp/index.html-
dc.relation.ispartofMolecular Pharmaceutics-
dc.rightsThis document is the Accepted Manuscript version of a Published Work that appeared in final form in [JournalTitle], copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see [insert ACS Articles on Request author-directed link to Published Work, see http://pubs.acs.org/page/policy/articlesonrequest/index.html].-
dc.subjectlung surfactant-
dc.subjectmonodisperse PEG-
dc.subjectPEGylation-
dc.subjectpeptide-
dc.subjectpulmonary delivery-
dc.titleOptimization of PEGylated KL4 Peptide for siRNA Delivery with Improved Pulmonary Tolerance-
dc.typeArticle-
dc.identifier.emailQiu, Y: qiuysh@hku.hk-
dc.identifier.emailWan, TLL: leonwan.cpos@hku.hk-
dc.identifier.emailLo, JCK: jasonlck@hku.hk-
dc.identifier.emailLam, JKW: jkwlam@hku.hk-
dc.identifier.authorityLam, JKW=rp01346-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1021/acs.molpharmaceut.0c01242-
dc.identifier.pmid34014665-
dc.identifier.scopuseid_2-s2.0-85107902693-
dc.identifier.hkuros322806-
dc.identifier.volume18-
dc.identifier.issue6-
dc.identifier.spage2218-
dc.identifier.epage2232-
dc.identifier.isiWOS:000661309800009-
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats