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Article: Plasmid DNA ionisable lipid nanoparticles as non-inert carriers and potent immune activators for cancer immunotherapy

TitlePlasmid DNA ionisable lipid nanoparticles as non-inert carriers and potent immune activators for cancer immunotherapy
Authors
KeywordsCancer immunotherapy
Combinatory
Lipid nanoparticles
Plasmid DNA
siRNA
Issue Date2024
Citation
Journal of Controlled Release, 2024, v. 369, p. 251-265 How to Cite?
AbstractImmunotherapy is currently a standard of care in the treatment of many malignancies. However, predictable side effects caused by systemic administration of highly immunostimulatory molecules have been a serious concern within this field. Intratumoural expression or silencing of immunogenic and immunoinhibitory molecules using nucleic acid-based approaches such as plasmid DNA (pDNA) and small interfering RNA (siRNA), respectively, could represent a next generation of cancer immunotherapy. Here, we employed lipid nanoparticles (LNPs) to deliver either non-specific pDNA and siRNA, or constructs targeting two prominent immunotherapeutic targets OX40L and indoleamine 2,3-dioxygenase-1 (IDO), to tumours in vivo. In the B16F10 mouse model, intratumoural delivery of LNP-formulated non-specific pDNA and siRNA led to strong local immune activation and tumour growth inhibition even at low doses due to the pDNA immunogenic nature. Replacement of these non-specific constructs by pOX40L and siIDO resulted in more prominent immune activation as evidenced by increased immune cell infiltration in tumours and tumour-draining lymph nodes. Consistently, pOX40L alone or in combination with siIDO could prolong overall survival, resulting in complete tumour regression and the formation of immunological memory in tumour rechallenge models. Our results suggest that intratumoural administration of LNP-formulated pDNA and siRNA offers a promising approach for cancer immunotherapy.
Persistent Identifierhttp://hdl.handle.net/10722/350046
ISSN
2023 Impact Factor: 10.5
2023 SCImago Journal Rankings: 2.157

 

DC FieldValueLanguage
dc.contributor.authorQin, Yue-
dc.contributor.authorRouatbi, Nadia-
dc.contributor.authorWang, Julie Tzu Wen-
dc.contributor.authorBaker, Rafal-
dc.contributor.authorSpicer, James-
dc.contributor.authorWalters, Adam A.-
dc.contributor.authorAl-Jamal, Khuloud T.-
dc.date.accessioned2024-10-17T07:02:42Z-
dc.date.available2024-10-17T07:02:42Z-
dc.date.issued2024-
dc.identifier.citationJournal of Controlled Release, 2024, v. 369, p. 251-265-
dc.identifier.issn0168-3659-
dc.identifier.urihttp://hdl.handle.net/10722/350046-
dc.description.abstractImmunotherapy is currently a standard of care in the treatment of many malignancies. However, predictable side effects caused by systemic administration of highly immunostimulatory molecules have been a serious concern within this field. Intratumoural expression or silencing of immunogenic and immunoinhibitory molecules using nucleic acid-based approaches such as plasmid DNA (pDNA) and small interfering RNA (siRNA), respectively, could represent a next generation of cancer immunotherapy. Here, we employed lipid nanoparticles (LNPs) to deliver either non-specific pDNA and siRNA, or constructs targeting two prominent immunotherapeutic targets OX40L and indoleamine 2,3-dioxygenase-1 (IDO), to tumours in vivo. In the B16F10 mouse model, intratumoural delivery of LNP-formulated non-specific pDNA and siRNA led to strong local immune activation and tumour growth inhibition even at low doses due to the pDNA immunogenic nature. Replacement of these non-specific constructs by pOX40L and siIDO resulted in more prominent immune activation as evidenced by increased immune cell infiltration in tumours and tumour-draining lymph nodes. Consistently, pOX40L alone or in combination with siIDO could prolong overall survival, resulting in complete tumour regression and the formation of immunological memory in tumour rechallenge models. Our results suggest that intratumoural administration of LNP-formulated pDNA and siRNA offers a promising approach for cancer immunotherapy.-
dc.languageeng-
dc.relation.ispartofJournal of Controlled Release-
dc.subjectCancer immunotherapy-
dc.subjectCombinatory-
dc.subjectLipid nanoparticles-
dc.subjectPlasmid DNA-
dc.subjectsiRNA-
dc.titlePlasmid DNA ionisable lipid nanoparticles as non-inert carriers and potent immune activators for cancer immunotherapy-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.jconrel.2024.03.018-
dc.identifier.pmid38493950-
dc.identifier.scopuseid_2-s2.0-85188967620-
dc.identifier.volume369-
dc.identifier.spage251-
dc.identifier.epage265-
dc.identifier.eissn1873-4995-

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