Gd(III) ion-chelated supramolecular assemblies composed of PGMA-based polycations for effective biomedical applications

Abstract

Ethanolamine (EA) or ethylenediamine (ED)-functionalized poly(glycidyl methacrylate) (PGMA), namely PGEA or PGED, has recently been used as effective gene carriers because of their low cytotoxicity and high transfection efficiency. In this study, a series of PGMA-based supramolecular polycations (PGED-Gd@PGEAs) with magnetic resonance imaging (MRI) functions were readily constructed by assembling multiple adamantine-headed star PGEA (Ad-PGEA) units with a versatile PGED-CD-Gd backbone, which possessed numerous flanking β-cyclodextrin species and Gd 3+ ions. The properties of different PGED-Gd@PGEA vectors were systematically characterized, including the plasmid DNA condensation ability, cytotoxicity, gene transfection efficiency, cellular uptake and MRI function. Such supramolecular gene vectors had lower toxicity than 'gold standard' polyethylenimine (PEI, 25 kDa). Furthermore, PGED-Gd@PGEAs exhibited significantly higher transfection efficiencies than PEI or the constituent units (PGED-CD-Gd and Ad-PGEA). The chelation of Gd 3+ ions imparted the PGED-Gd@PGEA vectors with a good MRI ability without obvious adverse effects. The present design of PGMA-based supramolecular polycations with Gd 3+ chelation would provide useful information for the development of low-toxicity and high-efficiency multifunctional gene delivery systems.

Biodegradable, multifunctional DNAzyme nanoflowers for enhanced cancer therapy

“…3 Recently, ribozymes, deoxyribozymes (DNAzymes), antisense oligonucleotides and short interfering RNAs have been actively investigated due to their potential application in gene inactivation or downregulation. [4][5][6] Among these therapeutic agents, DNAzymes, which can be engineered to bind to complementary sequences in a target messenger RNA (mRNA) and then cleave it at predetermined phosphodiester linkages, are particularly attractive due to their easy, low-cost synthesis, high selectivity and significant catalytic efficiency. [7][8][9] Despite the increasing interest in DNAzyme-mediated gene silencing as a therapeutic strategy, safety and efficiency remain the critical hurdles to overcome for practical applications.…”

Flexible Cationic Nanoparticles with Photosensitizer Cores for Multifunctional Biomedical Applications

“…The plasmid DNA (pDNA) condensation ability of the prepared PRPs at different weight ratios (w/w) was analyzed by agarose gel electrophoresis as described in our earlier work . Figure a shows that PRP1 is able to condense pDNA well at the weight ratio of 2.5, while PRP2 and PRP3 exhibit similar condensation abilities at the weight ratio of 1.5.…”

“…The transfection performance of PRP was first analyzed with the reporter gene pDNA including encoding Renilla luciferase (pRL‐CMV) in the selected HEK293, HepG2 and 4T1 cell lines at various mass ratios, where the branched PEI (25 kDa) at its optimal N/P ratio of 10 was taken as the control . As shown in Figure b, the optimal transfection efficiencies were observed at the weight ratio of 40.…”

“…The particle sizes and zeta potential of PRP/pDNA complexes were investigated via a Zetasizer Nano ZS system. The morphologies of complexes at the weight ratio of 40 were observed using AFM as described in our earlier work …”

Multi-arm carriers composed of an antioxidant lignin core and poly(glycidyl methacrylate-co-poly(ethylene glycol)methacrylate) derivative arms for highly efficient gene delivery

“…[35][36][37][38][39] PEGMA was incorporated into the system to enhance the water solubility and to improve the stability of the polyplexes under serum conditions. PGEA has been widely explored as an alternative cationic segment for gene delivery with a better cell viability profile compared with poly(di-methyl-aminoethylmethacrylate) (PDMAEMA) and polyethyleneimine (PEI).…”