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Antagonist G-targeted liposomes for improved delivery of anticancer drugs in small cell lung carcinoma

2022-01Journal article Open access
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dc.contributor.authorCarvalheiro, Manuela
dc.contributor.authorFerreira-Silva, Margarida
dc.contributor.authorHolovanchuk, Denys
dc.contributor.authorMarinho, H. Susana
dc.contributor.authorMoreira, João Nuno
dc.contributor.authorSoares, Helena
dc.contributor.authorCorvo, M. Luisa
dc.contributor.authorCruz, Maria Eugénia M.
dc.date.accessioned2022-03-04T13:23:42Z
dc.date.available2024-03-01T01:30:21Z
dc.date.issued2022-01
dc.descriptionFCT_UID/Multi/00612/2019. FCT_UIDB/00100/2020. FCT_UIDP/00100/2020.pt_PT
dc.description.abstractLigand-mediated targeted liposomes have the potential to increase the therapeutic efficacy of anticancer drugs. This work aimed to evaluate the ability of antagonist G, a peptide targeting agent capable of blocking the action of multiple neuropeptides, to selectivity improve targeting and internalization of liposomal formulations (long-circulating liposomes, LCL, and stabilized antisense lipid particles containing ionizable amino lipid, SALP) to H69 and H82 small cell lung carcinoma (SCLC) cell lines. Antagonist G-targeted LCL and SALP were prepared by two different methods (either by direct covalent linkage at activated PEG grafted onto the liposomal surface or by post-insertion of DSPE-PEG-antagonist-G-conjugates into pre-formed liposomes). Association of the liposomal formulations with target SCLC cells was studied by fluorescence microscopy using fluorescence-labeled liposomes and confirmed quantitatively with [3H]-CHE-labelled liposomes. An antisense oligodeoxynucleotide against the overexpressed oncogene c-myc(as(c-myc)) was efficiently loaded into SALP formulations, the encapsulation efficiency decreased due to the inclusion of the targeting ligand. Also, liposome size was affected by as(c-myc) physical-chemical properties. The amount of antagonist G linked to the surface of the liposomal formulations was dependent on the coupling method and lipid composition used. Covalent attachment of antagonist G increased liposomes' cellular association and internalization via receptor-mediated and clathrin-dependent endocytosis, as assessed in SCLC cell lines. Biodistribution studies in healthy mice revealed a preferential lung accumulation of antagonist G-targeted SALP as compared to the non-targeted counterpart. Lung levels of the former were up to 3-fold higher 24 h after administration, highlighting their potential to be used as delivery vectors for SCLC treatment.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCarvalheiro M, Ferreira-Silva M, Holovanchuk D, Marinho S, Moreira JN, Soares H, et al. Antagonist G-targeted liposomes for improved delivery of anticancer drugs in small cell lung carcinoma. Int J Pharmaceutics. 2022;612:121380.pt_PT
dc.identifier.doi10.1016/j.ijpharm.2021.121380pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.21/14382
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationFCT_UID/Multi/00612/2019pt_PT
dc.relationFCT_UIDB/00100/2020pt_PT
dc.relationFCT_UIDP/00100/2020pt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S0378517321011868pt_PT
dc.subjectAntineoplastic agentspt_PT
dc.subjectTherapeutic usept_PT
dc.subjectDrug delivery systemspt_PT
dc.subjectLiposomespt_PT
dc.subjectLung neoplasmspt_PT
dc.subjectDrug therapypt_PT
dc.subjectOligopeptidespt_PT
dc.subjectSmall cell lung carcinomapt_PT
dc.subjectTissue distributionpt_PT
dc.subjectFCT_UID/Multi/00612/2019pt_PT
dc.subjectFCT_UIDB/00100/2020pt_PT
dc.subjectFCT_UIDP/00100/2020pt_PT
dc.titleAntagonist G-targeted liposomes for improved delivery of anticancer drugs in small cell lung carcinomapt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.startPage121380pt_PT
oaire.citation.titleInternational Journal of Pharmaceuticspt_PT
oaire.citation.volume612pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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