Experimental design and characterization of dual-antibody-conjugated all-trans retinoic acid-loaded lipid nanoparticles as a potential cancer therapy

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dc.contributor.authorIslek, Zeynep
dc.contributor.authorSagiroglu, Ali Asram
dc.contributor.authorUcisik, Mehmet Hikmet
dc.contributor.authorKirbas, Oguz Kaan
dc.contributor.authorDemirel, Erhan
dc.contributor.authorYurdasiper, Aysu
dc.contributor.authorSahin, Fikrettin
dc.date.accessioned2024-08-31T07:50:27Z
dc.date.available2024-08-31T07:50:27Z
dc.date.issued2024
dc.departmentEge Üniversitesien_US
dc.description.abstractAntibody-targeted immunotherapy has emerged in cancer therapies regarding checkpoint inhibition with monoclonal antibodies, such as anti-programmed death-ligand 1 (anti-PD-L1) either given alone or in combination. However, when given alone, it may fail to activate tumor-specific T cells. The combinational therapy of anti-PD-L1 with anti-4-1BB and all-trans retinoic acid (ATRA) has come into prominence due to disease heterogeneity, resulting in the synergistic effects associated with greater T-cell responses. This study introduces antiPD-L1 and anti-4-1BB-conjugated ATRA-loaded solid lipid nanoparticles (SLNs), where the Design-Expert Program was applied for the optimization. Accordingly, antibody-conjugated ATRA-loaded SLNs had uniform dispersions with mean diameters of 179.6 f 12.6 nm. The formulations achieved the encapsulation efficiency (EE %) of ATRA at 21.2 f 1.4 %, regarding the three-dimensional response surface graph. The binding efficiency of anti-4-1BB and anti-PD-L1 antibodies were determined as 85.59 f 7.3 % and 90.02 f 5.4 %, respectively. The release profile of formulations indicated the biphasic release of ATRA (ie., 76 f 4.4%) from SLNs within 24 h via the Higuchi model. Particle size distributions of SLNs displayed a 7 % increase (i.e., 190.5 f 7.63 nm) at 4 degrees C over 2 months. The experimental design of anti-PD-L1- and anti-4-1BB-conjugated- ATRA-loaded SLNs highlighted the promising strategy for the development of alternative formulations and the potential approach for further cancer therapies.en_US
dc.description.sponsorshipYeditepe University, Turkiyeen_US
dc.description.sponsorshipThe financial support was provided by Yeditepe University, Turkiye. The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.en_US
dc.identifier.doi10.1016/j.jddst.2024.105995
dc.identifier.issn1773-2247
dc.identifier.issn2588-8943
dc.identifier.scopus2-s2.0-85200490102en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1016/j.jddst.2024.105995
dc.identifier.urihttps://hdl.handle.net/11454/105225
dc.identifier.volume100en_US
dc.identifier.wosWOS:001290634700001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.ispartofJournal of Drug Delivery Science and Technologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.snmz20240831_Uen_US
dc.subjectSolid Lipid Nanoparticles (Slns)en_US
dc.subjectAnti-Programmed Death-Ligand 1 (Anti-Pd-L1)en_US
dc.subjectAll-Trans Retinoic Acid (Atra)en_US
dc.subjectAnti-4-1bben_US
dc.subjectAntibody Conjugationen_US
dc.subjectSurface Modificationen_US
dc.titleExperimental design and characterization of dual-antibody-conjugated all-trans retinoic acid-loaded lipid nanoparticles as a potential cancer therapyen_US
dc.typeArticleen_US

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