Polyvalent Display of Monosaccharides on Ferritin Protein Cage Nanoparticles for the Recognition and Binding of Cell‐Surface Lectins

Abstract

Carbohydrate-lectin interactions are important in many biological events. Endogenous cell-surface lectins are attractive markers for the recognition and targeting. Human ferritin protein cage nanoparticles (HFPCNs) are prepared as delivery nanoplatforms and two different types of monosaccharide derivatives; maleimido group terminated-mannopyranoside and galactopyranoside. Uniform and polyvalent displays of mannoses or galactoses on the surface of HFPCNs are achieved by using site-specific thiol-maleimide Michael-type addition. Mannose- or galactose-displaying HFPCNs recognize and tightly bind to DC-SIGN or ASGP-R lectins on the surface of the mammalian cells, DCEK or HepG2 cells.

Lumazine Synthase Protein Nanoparticle-Gd(III)-DOTA Conjugate as a T1 contrast agent for high-field MRI

“…Protein cage nanoparticles, including ferritins, encapsulins, and virus-like particles (VLPs), have been widely used as nanoscale delivery vehicles for diagnostic and/or therapeutic reagents 9 10 11 12 13 14 15 16 17 18 19 20 21 as they not only have well-defined structure and size, but also consist of biocompatible and biodegradable biomaterials, polypeptides 22 . The highly symmetrical and uniformly composed architecture of protein cage nanoparticles allow them to be manipulated in a highly controlled manner, resulting in the production of reproducible nanoscale multifunctional particles 9 10 11 12 13 14 15 16 17 18 19 20 21 . VLPs have been extensively studied as supramolecular templates for the conjugation of small molecule contrast agents, such as the chelated paramagnetic gadolinium ion (Gd(III)), which is frequently used as a positive contrast agent for magnetic resonance imaging (MRI) 23 24 25 26 27 .…”

Molecular Display on Protein Nanocompartments: Design Strategies and Systems Applications

“…The most popular method of thiol functionalisation is through Michael addition onto maleimides. The reaction between thiols and maleimides has been used to attach dyes, [28,51,[54][55][56] peptides, [55] carbohydrates, [57] DNA, [58] and metals [59] to the outside of nanocompartment shells. In comparison to amine conjugation, there are generally less surface-exposed thiols than amines, resulting in a higher degree of control and lower stoichiometry of functionalisation.…”

Ferritin nanocages: A biological platform for drug delivery, imaging and theranostics in cancer

“…Despite the natural targeting of ferritin towards cancer cells, several research groups have modified the surface of ferritin nanocages by inserting a number of target motifs, such as antibodies, peptides and antibody fragments, in order to drive nanoparticles towards specific cells by selective recognition (Figure 1). Both lysines and cysteines on the ferritin surface have been exploited for chemical conjugation using different heterobifunctional cross-linkers with N-hydroxysuccinimide (NHS) ester and maleimide groups [42][43][44]. Lys and Cys residues have also been employed to chemically attach dyes, quencher molecules or polyethylene glycol (PEG) molecules [22,45].…”

“…Some research groups have taken advantage of the ability of H-ferritin to specifically recognize TfR1 [33], a receptor expressed on the surface of many types of cancer cells [41]. Other groups have chemically or genetically inserted targeting motifs onto the ferritin surface, to improve tumor homing [42][43][44][45][46][47][48][49][50][51][52][53][54]. This strategy has been demonstrated to be very promising, since targeted therapies are probably the key for cancer treatment [96].…”