Experimental design and characterization of dual-antibody-conjugated all-trans retinoic acid-loaded lipid nanoparticles as a potential cancer therapy
Küçük Resim Yok
Tarih
2024
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Antibody-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.
Açıklama
Anahtar Kelimeler
Solid Lipid Nanoparticles (Slns), Anti-Programmed Death-Ligand 1 (Anti-Pd-L1), All-Trans Retinoic Acid (Atra), Anti-4-1bb, Antibody Conjugation, Surface Modification
Kaynak
Journal of Drug Delivery Science and Technology
WoS Q Değeri
N/A
Scopus Q Değeri
Q1
Cilt
100
