(414f) Multicomponent Folate-Targeted Magnetoliposomes: Design, Characterization, and Preliminary in Vitro Hela Cell Studies

Overexpression of folate receptor (FR) is common to many cancer cell lines and provides a means of targeting nanoscale therapeutics. This presentation will describe the design, characterization, and preliminary cytotoxicity results of folate-targeted cationic magnetoliposomes (FTMLs), stabilized by electrostatic and steric repulsion, containing co-encapsulating doxorubicin (DOX, 2 μM) and anionic superparamagnetic iron oxide (SPIO, 1 μM) nanoparticles. The FTMLs were designed to achieve combined DOX delivery and hyperthermia under alternating current electromagnetic fields operating at radiofrequencies. By associating the SPIO nanoparticles (5 nm core Fe₂O₃ diamater) with the cationic bilayer through electrostatic attraction, localized nanoparticle heating at the liposome bilayer also provided a mechanism for triggering DOX release. Cryogenic transmission electron microscopy (cryo-TEM) analysis revealed the coexistence of unilamellar and cup-shaped FTML structures, 174 ± 53 nm in diameter, and confirmed that the nanoparticle were encapsulated. This analysis also showed that the FTMLs underwent structural changes after preparation, but retained their cargo. The presence of cup-shaped liposomes with regions of negative bilayer curvature is attributed to bilayer asymmetry and possible domain formation drive by differences in lipid packing parameters. Preliminary in vitro studies conducted on cervical cancer cells (HeLa) confirmed FR targeting and the synergistic effects of DOX delivery and hyperthermia on HeLa cell viability and morphology. While these studies were conducted as a proof-of-concept, to our knowledge this is the first report of FR-targeted magnetoliposome cellular delivery.