Akademik Veri Yönetim Sistemi
ACS Omega, cilt.11, sa.9, ss.15028-15043, 2026 (SCI-Expanded, Scopus)
Interleukin-2 (IL-2) is an immunostimulatory cytokine that stimulates T cells, natural killer cells, and other leukocytes, functioning as a growth factor. IL-2 interacts with IL-2Rα, IL-2Rβ, and γc receptors. IL-2 mediates its therapeutic effects by interacting with the β and γ receptor subunits against cancer, whereas interaction with the α, β, and γ receptor complexes is critical for treating autoimmune disorders. Current efforts aim to develop improved IL-2 biobetters that reduce toxicity through lower dosing strategies, particularly by blocking or slowing the interaction with IL-2Rα. According to these strategies, this study aimed to design a lipid-based IL-2 formulation that could modulate or partially prevent IL-2Rα binding, thereby enhancing the βγ-mediated antitumor efficacy while minimizing α-associated immune activation. Molecular dynamics (MD) simulates the physical motions of atoms and molecules in large systems containing thousands of atoms and is widely used in biotechnological drug formulations. In this study, MD was used to simulate time-dependent interactions between IL-2 and excipients of the lipid-based formulations to determine suitable excipients. Desmond was used to simulate and observe the temporal interactions between the formulation contents and IL-2. Interactions with Arg38, Phe42, and Leu72─key residues of the α-subunit interface─were specifically examined. According to the simulation analyses, polar side chains were protected by lipids, while no incompatibility was expected for the selected excipients. Interactions were observed with Arg38, which interacts with IL-2Rα; thus, an enhanced antitumor effect might be achieved. In addition to the in silico studies, in vitro cell culture experiments were conducted to examine the biological activity and anticancer efficacy of IL-2-loaded nanoemulsions. These studies demonstrated that IL-2’s biological activity was preserved, and its anticancer effect was enhanced against renal carcinoma cells. Overall, the results suggest that the formulation stabilizes IL-2 and enhances its α-targeted antitumor mechanism through rational excipient–protein interactions.