Dendrimer-protein interactions versus dendrimer-based nanomedicine

Abstract

Dendrimers are hyperbranched polymers belonging to the huge class of nanomedical devices. Their wide application in biology and medicine requires understanding of the fundamental mechanisms of their interactions with biological systems. Summarizing, electrostatic force plays the predominant role in dendrimer-protein interactions, especially with charged dendrimers. Other kinds of interactions have been proven, such as H-bonding, van der Waals forces, and even hydrophobic interactions. These interactions depend on the characteristics of both participants: flexibility and surface charge of a dendrimer, rigidity of protein structure and the localization of charged amino acids at its surface. pH and ionic strength of solutions can significantly modulate interactions. Ligands and cofactors attached to a protein can also change dendrimer-protein interactions. Binding of dendrimers to a protein can change its secondary structure, conformation, intramolecular mobility and functional activity. However, this strongly depends on rigidity versus flexibility of a protein's structure. In addition, the potential applications of dendrimers to nanomedicine are reviwed related to dendrimer-protein interactions.

Sistemas de Nanopartículas Poliméricas II: Estructura, Métodos de Elaboración, Características, Propiedades, Biofuncionalización y Tecnologías de Auto-Ensamblaje Capa por Capa (Layer-by-Layer Self-Assembly)

“…La fuerza electrostática desempeña el papel predominante en las interacciones dendrímero-proteína, especialmente con dendrímeros cargados, se han demostrado otros tipos de interacciones como el enlace H, las fuerzas de van der Waals e incluso las interacciones hidrofóbicas. La unión de dendrímeros a una proteína puede cambiar su estructura secundaria, conformación, movilidad intramolecular y actividad funcional (Shcharbin et al, 2017).…”

Modulating protein amyloid aggregation with nanomaterials

“…94,90 It has been found that altering polymer hydrophobicity and net surface charge can modulate their action on protein amyloid aggregation. 59,71,92,93 As synthetic polymers such as NiPAM/BAM and dendrimers are utilized for drug delivery, the fact that their design may potentially have a downstream impact on amyloid aggregation in vivo should be taken into consideration. 92,93 A similar phenomenon has also been observed for superparamagnetic iron oxide NPs (SIONPs), where positively charged SIONPs were capable of promoting amyloid fibrillization compared with negatively charged or uncharged SIONPs at the same concentration.…”

“…59,71,92,93 As synthetic polymers such as NiPAM/BAM and dendrimers are utilized for drug delivery, the fact that their design may potentially have a downstream impact on amyloid aggregation in vivo should be taken into consideration. 92,93 A similar phenomenon has also been observed for superparamagnetic iron oxide NPs (SIONPs), where positively charged SIONPs were capable of promoting amyloid fibrillization compared with negatively charged or uncharged SIONPs at the same concentration. 59 With amino-modified polystyrene NPs, Cabaleiro-Lago et al observed acceleration and inhibition of Aβ fibrillization in the presence of NPs with small and large surface areas, respectively.…”

“…139 As discussed previously, NPs with drug delivery capabilities such as NiPAM/BAM and dendrimers possess anti-amyloid properties themselves. 92,93 It is a promising strategy to load anti-amyloid small-molecule inhibitors by utilizing their encapsulation ability or directly conjugating natural amyloid inhibitors around their surface to achieve a boosted anti-amyloid effect on designated targets.…”

Immunoreactivity changes of human serum albumin and alpha-1-microglobulin induced by their interaction with dendrimers

“…Serum albumins are the main transport proteins in plasma (50-60% of total plasma proteins), giving an FW of 66 kDa [16][17][18]. Albumins can bind anionic and cationic ligands with high affinity due to the presence of charged groups and hydrophobic pockets in their structure, and due to their negative surface charge [16][17][18][19][20]. Human alpha-1-microglobulin (A1M) is a glycoprotein of˜30 kDa present in blood plasma and some tissues of the human body [17,21].…”