Hydrogels of Polycationic Acetohydrazone-Modified Phosphorus Dendrimers for Biomedical Applications: Gelation Studies and Nucleic Acid Loading

Abstract

In this work, we report the assemblage of hydrogels from phosphorus dendrimers in the presence of biocompatible additives and the study of their interactions with nucleic acids. As precursors for hydrogels, phosphorus dendrimers of generations 1–3 based on the cyclotriphosphazene core and bearing ammonium or pyridinium acetohydrazones (Girard reagents) on the periphery have been synthesized. The gelation was done by the incubation of dendrimer solutions in water or phosphate-buffered saline in the presence of biocompatible additives (glucose, glycine or polyethylene glycol) to form physical gels. Physical properties of gels have been shown to depend on the gelation conditions. Transmission electron microscopy revealed structural units and well-developed network structures of the hydrogels. The hydrogels were shown to bind nucleic acids efficiently. In summary, hydrogels of phosphorus dendrimers represent a useful tool for biomedical applications.

In Vitro Validation of the Therapeutic Potential of Dendrimer-Based Nanoformulations against Tumor Stem Cells

“…Cationic phosphorus dendrimers, i.e., dendrimers containing phosphorus atoms as core and branching points, show promise for the antitumor therapy as carriers for therapeutic oligonucleotides and also as bioactive entities both as agents for drug delivery [ 9 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ] and as nanodrugs per se [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. The former option is realized due to the presence of multiple cationic groups on the periphery of dendritic molecules that provide efficient oligonucleotide binding and protection against serum nucleases.…”

Dendriplex-Impregnated Hydrogels With Programmed Release Rate

“…The structures of dendrimers are given in Figure 1 . Dendrimers TG3 and PG3 can form hydrogels through multiple hydrogen bonds between branches, with biomimetic additives facilitating the gelation ( Marmillon et al, 2001 ; Apartsin et al, 2018 ). Such dendrimer hydrogels were able to bind oligonucleotides reversibly.…”

“…Polycationic phosphorus dendrimers were synthesized according to previously published procedures ( Ihnatsyeu-Kachan et al, 2017 ; Apartsin et al, 2018 ). Mcl-1 siRNA (sense strand: 5′-GGACUUUUAUACCUGUUAUtt-3′-FAM; antisense strand: 5′-AUA​ACA​GGU​AUA​AAA​GUC​Ctg; lowercase letters denote deoxyribonucleotides) was synthesized and annealed as described in Krasheninina et al (2019 ).…”

Dendrimers Functionalized with Palladium Complexes of N-, N,N-, and N,N,N-Ligands

“…The problem is presumably due to the hydrazide linkage which may induce multiple hydrogen bonding. We have already demonstrated that other types of hydrazide derivatives (namely P and T Girard’s reagents) linked to phosphorhydrazone dendrimers or dendrons induced the spontaneous formation of hydrogels in water [ 28 , 29 , 30 , 31 ], characteristic of a decreased solubility of the dendrimer. Furthermore, the packing in the crystal structure of compound 5 ( Figure 7 B) has pointed out the presence of such interactions, in a head to tail arrangement, which will favor the interactions between dendrimers, thus decreasing largely the solubility.…”