Bovine Lactoferrin Loaded Magnetic-Responsive Plasmonic Lipo-Somes for Therapeutic Applications

Abstract

Bovine lactoferrin (bLf) is a milk-derived protein that exhibits multiple biological activities and has been explored towards different therapeutic applications. Since this molecule is susceptible to degradation and some of its properties depend on its tertiary structure, the encapsulation of bLf in stimuli-responsive therapeutic formulations provides an added value to potentiate its biological activities when administered. Plasmonic magnetoliposomes emerge as promising nanosystems for dual hyperthermia (magneto-photothermia) and local therapy, since the combination of magnetic and gold nanoparticles (NPs) in a single nanosystem (multifunctional liposomes) enables the targeting and controlled release of encapsulated drugs. In this work, plasmonic magnetoliposomes (PMLs) containing manganese ferrite nanoparticles (28 nm size) and gold nanoparticles (~ 5 nm size) functionalized with 11-mercaptoundecanoic acid or octadecanethiol, were synthesized and loaded with bLf. The structural, magnetic and optical properties of the nanoparticles were measured by TEM, SQUID and UV/vis/NIR absorption spectroscopy. Specific Absorption Rate was determined to assess the capabilities for magnetic and photothermal hyperthermia. Finally, Saccharomyces cerevisiae was used as an eukaryotic cellular model to assess the biological activity and the mechanism of entry of bLf-loaded PMLs, through counting of colony forming units and fluorescence microscopy, respectively. The results demonstrate that PMLs are mainly internalized through an energy- and temperature-dependent endocytic process, though the contribution of a diffusion component cannot be discarded. Most notably, only bLf-loaded PMLs exhibit cytotoxicity with an efficiency similar to free bLf, attesting their promising potential for bLf delivery in the context of therapeutic interventions.