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

dc.authorid0000-0002-4634-3864
dc.contributor.authorİşlek, Zeynep
dc.contributor.authorSağıroğlu, Ali Asram
dc.contributor.authorÜçışık, Mehmet Hikmet
dc.contributor.authorKırbaş, Oğuz Kaan
dc.contributor.authorDemirel, Erhan
dc.contributor.authorYurdasiper, Aysu
dc.contributor.authorŞahin, Fikrettin
dc.contributor.authorÖzer, Özgen
dc.date.accessioned2024-09-20T11:42:02Z
dc.date.available2024-09-20T11:42:02Z
dc.date.issued2024
dc.departmentİstanbul Medipol Üniversitesi, Mühendislik ve Doğa Bilimleri Fakültesi, Biyomedikal Mühendisliği Bölümü
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 anti-PD-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 ± 12.6 nm. The formulations achieved the encapsulation efficiency (EE %) of ATRA at 21.2 ± 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 ± 7.3 % and 90.02 ± 5.4 %, respectively. The release profile of formulations indicated the biphasic release of ATRA (ie., 76 ± 4.4 %) from SLNs within 24 h via the Higuchi model. Particle size distributions of SLNs displayed a 7 % increase (i.e., 190.5 ± 7.63 nm) at 4 °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.
dc.description.sponsorshipYeditepe University, Turkiyeen_US
dc.identifier.citationİşlek, Z., Sağıroğlu, A. A., Üçışık, M. H., Kırbaş, O. K., Demirel, E., Yurdasiper, A. ... Özer, Ö. (2024). Experimental design and characterization of dual-antibody-conjugated all-trans retinoic acid-loaded lipid nanoparticles as a potential cancer therapy. Journal of Drug Delivery Science and Technology, 100. http://dx.doi.org/10.1016/j.jddst.2024.105995
dc.identifier.doi10.1016/j.jddst.2024.105995
dc.identifier.issn1773-2247
dc.identifier.issn2588-8943
dc.identifier.scopus2-s2.0-85200490102
dc.identifier.scopusqualityQ1
dc.identifier.urihttp://dx.doi.org/10.1016/j.jddst.2024.105995
dc.identifier.urihttps://hdl.handle.net/20.500.12511/12819
dc.identifier.volume100
dc.identifier.wos001290634700001en_US
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.institutionauthorDemirel, Erhan
dc.language.isoen
dc.relation.ispartofJournal of Drug Delivery Science and Technologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectAll-Trans Retinoic Acid (ATRA)
dc.subjectAnti-4-1BB
dc.subjectAnti-Programmed Death-Ligand 1 (Anti-PD-L1)
dc.subjectAntibody Conjugation
dc.subjectSolid Lipid Nanoparticles (Slns)
dc.subjectSurface Modification
dc.titleExperimental design and characterization of dual-antibody-conjugated all-trans retinoic acid-loaded lipid nanoparticles as a potential cancer therapy
dc.typeArticle

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