Lactoferrin as a Versatile Agent in Nanoparticle Applications: From Therapeutics to Agriculture

Abstract

Nanoparticles (NPs) have emerged as a potent choice for various applications, from drug delivery to agricultural studies, serving as an alternative and promising methodology for future advancements. They have been widely explored in delivery systems, demonstrating immense promise and high efficiency for the delivery of numerous biomolecules such as proteins and anticancer agents, either solely or modified with other compounds to enhance their capabilities. In addition, the utilization of NPs extends to antimicrobial studies, where they are used to develop novel antibacterial, antifungal, and antiviral formulations with advanced characteristics. Lactoferrin (Lf) is a glycoprotein recognized for its significant multifunctional properties, such as antimicrobial, antioxidant, anti-inflammatory, anticancer, and neuroprotective effects. Its activity has a broad distribution in the human body, with Lf receptors present in multiple regions. Current research shows that Lf is utilized in NP technology as a surface material, encapsulated biomolecule, and even as an NP itself. Due to the abundance of Lf receptors in various regions, Lf can be employed as a surface material in NPs for targeted delivery strategies, particularly in crossing the BBB and targeting specific cancers. Furthermore, Lf can be synthesized in an NP structure, positioning it as a strong candidate in future NP-related applications. In this article, we explore the highlighted and underexplored areas of Lf applications in NPs research.

Keywords: agriculture; anticancer; antimicrobial activity; drug delivery; lactoferrin; nanoparticles; neuroprotection; toxicity.

Figure 2

Functionalization methods for obtaining Lf-conjugated NPs for drug delivery strategies [40]. (A) Positively charged residues of Lf can adsorb onto negatively charged NPs in an aqueous medium, forming Lf-coated nanocarriers for drug delivery applications. (B) Depending on the crosslinking agent used, Lf can be covalently bound to NPs through coupling reactions. Crosslinking agents activate necessary functional groups to enable the formation of covalent bonds between Lf and NP. (C) A simpler method involves conjugating Lf to NPs by adding dissolved particles dropwise into an Lf solution. (D) Using activating reagents, amine groups on the surface of NPs can be activated, enabling Lf to react with the activated carriers for coating.

Figure 4

Drug delivery with Lf-conjugated NPs. Lf-conjugated NPs can cross the BBB with receptor-mediated transcytosis, delivering both NPs and encapsulated biomolecules at the target location. Lf can also be delivered with encapsulation into NPs, enhancing its biological activities [71,72].

Figure 5

Schematic illustration depicting the potential pathways of antiviral activity by Lf and Lf-modified NPs. (A) Lf can be swallowed by endocytosis; the interaction of Lf-modified NPs needs validation. (B) The endocytosis of Lf-modified NPs needs validation. (C) Lf or Lf-modified NPs can inhibit HSV-1/2 infection by binding to heparan sulfate moieties found in the glycoproteins of the cell surface and extracellular matrix. (D) Lf or Lf-modified NPs can obstruct viral binding by attaching to the virus attachment ligands (VALs), thus preventing the virus from connecting to its particular receptor(s) [115].

Figure 1

General properties of Lf and Lf-modified NPs [4,7,11].

Figure 3

General mechanism of drug delivery of Lf NPs [66].

Figure 6

Potential toxicity of NPs and Lf. The toxicity capacity of NPs depends on not only the type of the NPs, but also the exposure time, concentration, and physicochemical properties, specifically their size. High-concentration and recombinantly produced Lf can cause potential adverse effects on the immune system. As a result, similar to most NP-based applications, the following toxicity mechanisms can be observed in Lf-based NP applications: ROS-mediated DNA damage, protein denaturation, lipid peroxidation, and mitochondrial dysfunction [28,171].