Lactoferrin, a unique molecule with diverse therapeutical and nanotechnological applications

Abstract

Lactoferrin (LF) is a naturally glycoprotein with iron-binding properties and diverse biological applications including; antiviral, anti-inflammatory, antioxidant, anti-cancer and immune stimulating effects. In addition, LF was found to be an ideal nanocarrier for some hydrophobic therapeutics because of its active targeting potential due to overexpression of its receptor on the surface of many cells. Moreover, it was proven to be a good candidate for fabrication of nanocarriers to specifically deliver drugs in case of brain tumors owing to the capability of LF to cross the blood brain barrier (BBB). Consequently, it seems to be a promising molecule with multiple applications in the field of cancer therapy and nanomedicine.

Lactoferrin in the Prevention and Treatment of Intestinal Inflammatory Pathologies Associated with Colorectal Cancer Development

“…Dietary Lf, included in both natural and supplemented foods, incurs in both enzymatic digestion and physical barriers of the gastrointestinal mucosa, which contribute to its poor permeability across the gut epithelium. To overcame this drawback, two strategies have been carried out: the administration of purified Lf (usually bLf) at higher dosage and, more recently, the development of new formulations of Lf aimed at improving its bioavailability [ 285 ]. In this regard, despite several studies have proven Lf to be safe and well-tolerated even at high dosages [ 286 , 287 ], Nguyen et al reported that the effect of bLf on the inflammatory balance of both intestinal epithelial cells and immature pig intestine is strictly dose-dependent.…”

A Review on Lactoferrin and Central Nervous System Diseases

“…Moreover, LfRs are overexpressed on the cellular surface of glioma [ 171 ], thus augmenting the specific uptake of Lf by cancer cells. There is sufficient evidence to support this concept, especially in gliomas [ 172 ]. Alternatively, Lf might be secreted by neoplastic astrocytes [ 171 ].…”

“…As a major iron-binding protein found in milk and other body fluids, Lf exerts antibacterial, antiviral, anti-inflammatory, immune-modulatory and anticarcinogenic effects [ 1 ]. Because of its ability to cross the BBB through LfR-mediated transcytosis processes within brain capillary endothelial cells [ 44 , 56 ] and its relatively good biocompatibility, safety, stability and resistance to proteolysis [ 5 ], the use of exogenous Lf as a therapeutic agent or the use of drug-loaded Lf-based nanoparticles were explored for the treatment of neurodegenerative diseases, cerebrovascular diseases, childhood developmental delays, brain tumors and other neurological-related diseases [ 57 , 172 , 173 ]. In fact, several unsolved questions emerge from studies including the bioavailability of Lf after oral administration, differences in physicochemical properties of commercially available Lf (in particularly the iron content), and difficulties in the clinical application (dosage, durations, evaluation of the outcomes), although it exerts pleiotropic biological functions and is safe and low-cost as a potential therapeutic agent [ 5 , 174 ].…”

Reduction of lactoferrin aggravates neuronal ferroptosis after intracerebral hemorrhagic stroke in hyperglycemic mice

“…These data suggest the role of Ltf in ferroptosis is complicated: it may depend on iron saturation statues (apo or holo form) of Ltf, and it may also have cell-specificity. Importantly, Ltf accesses the blood bran barrier (BBB) via receptor-mediated transcytosis, because Ltf receptors are highly expressed on the surface of the brain endothelial cells [ 75 , 76 ]. Additionally, research shows that orally and intravenously administered recombinant human Ltf had similarities in the up-regulation of specific genes involved in oxidative stress and inflammatory responses for both routes of treatments [ 77 ].…”