Novel Anticancer Triple Formula Based on Aptamer-Conjugated PEGylated Nanoliposomes

BackgroundCancer remains a leading cause of death worldwide, necessitating the development of affordable and innovative therapies to reduce its human and economic burden.ObjectivesIn this study, we aimed to develop a synergistic anticancer formula encapsulated in nanoliposomes to enhance efficacy and minimize side effects. Additionally, we explored the effect of aptamer conjugation on the efficacy and stability of the formula.MethodsThe Etoricoxib-β-cyclodextrin complex was prepared using the kneading method, and nanoliposomes were developed via thin film hydration. The AS1411 aptamer was conjugated to the nanoliposomes to target nucleolin, a protein overexpressed in cancer cells. The etoricoxib-β-cyclodextrin complex was characterized using proton nuclear magnetic resonance, and various liposome properties, including size, encapsulation efficiency, and stability, were optimized. The release profiles of the active compounds were evaluated using high-performance liquid chromatography, and their cytotoxicity was assessed in human cancer cell lines.ResultsThe nanoliposomes co-loaded with the three agents and their aptamer-conjugated counterpart showed optimal characteristics, with particle sizes of 133.3 ± 1.45 nm and 174.8 ± 4.78 nm, and zeta potentials of -15.26 ± 1.80 mV and -15.66 ± 2.57 mV, respectively. The encapsulation efficiencies were 88.63% (raloxifene), 41.73% (etoricoxib), and 39.26% (naringin) without the aptamer, and 81.99%, 36.66%, and 38.33%, respectively, with the aptamer. The IC₅₀ of the formula for the three co-loaded agents was 167.4 µg/mL for A549 cells and 2.6 µg/mL for MCF-7 cells. Cytotoxicity was further enhanced using their aptamer conjugate, particularly against the MDA-MB-231 cell line.ConclusionThe novel triple-drug-loaded, aptamer-conjugated nanoliposome formula may be a future cancer treatment strategy.