Chiral Recognition of Homochiral Poly (amidoamine) Dendrimers Substituted with R- and S-Glycidol by Keratinocyte (HaCaT) and Squamous Carcinoma (SCC-15) Cells In Vitro

Abstract

The generation 2 and 3 poly(amidoamine) dendrimers (PAMAM G2 and G3) were converted into N-(2,3-dihydroxy)propyl derivatives by the addition of enantiomerically pure S- and R-glycidol. The homochiral dendrimers bind to HaCaT and SCC-15 cell membranes with an R/S glycidol enantioselectivity ratio of 1.5:1, as was quantitatively determined by fluorescence microscopy and visualized by confocal microscopy. Fully substituted G2 and G3 dendrimers were equipped with 32 and 64 N-(2,3-dihydroxy)propyl residues and showed effectively radial symmetry for homochiral derivatives in 13C NMR spectrum in contrary to analogs obtained by reaction with rac-glycidol. The sub-stoichiometric derivatives of G2 and G3 were also obtained in order to characterize them spectroscopically. The homochiral dendrimers were labeled with two different fluorescent labels, fluorescein, and rhodamine B, using their isothiocyanates to react with G2 and G3 followed by the addition of S- and R-glycidol. Obtained fluorescent derivatives were deficiently filled with N-(2,3-dihydroxy)propyl substituents due to steric hindrance imposed by the attached label. Nevertheless, these derivatives were used to determine their ability to bind to the cell membrane of human keratinocytes (HaCaT) and squamous carcinoma cells (SCC-15). Confocal microscopy images obtained from cells treated with variously labeled conjugates and fluorescence analysis with fluorescence reader allowed us to conclude that R-glycidol derivatives were bound and entered the cells preferentially, with higher accumulation in cancer cells. The G3 polyamidoamine (PAMAM)-based dendrimers were taken up more efficiently than G2 derivatives. Moreover, S- and R-glycidol furnished dendrimers were highly biocompatible with no toxicity up to 300 µM concentrations, in contrast to the amine-terminated PAMAM analogs.

β-Cyclodextrin and Oligoarginine Peptide-Based Dendrimer-Entrapped Gold Nanoparticles for Improving Drug Delivery to the Inner Ear

“…Compared to other common nanocarriers for drug-targeted delivery, such as solid lipid nanoparticles, micelles, and polymeric nanoparticles, PAMAM dendrimers are nonimmunogenic and have controlled molecular architecture and uniform particle size ( Eichman et al, 2000 ). In addition, their internal cavity structure can improve the dispersibility of loaded drugs, and a large number of external end groups (-NH2, -COOH, and -OH surface groups) can be used to realize different targeting molecular ligands and fluorescent probe modifications ( Parimi et al, 2010 ; Malinga-Drozd et al, 2021 ). Poly amidoamine (PAMAM) dendrimers can be modified with various groups with different functions ( Tomalia et al, 1985 ; Tomalia et al, 1986 ), such as fluorophores, targeting ligands, and drugs, thereby expanding their applications to a variety of biological diagnostics and therapeutics ( Shakhbazau et al, 2010 ; Labieniec-Watala and Watala, 2015 ).…”

Safety Challenges and Application Strategies for the Use of Dendrimers in Medicine

“…In 2004, Ghorai et al were the first to introduce anthracene-capped chiral dendrimers with 1,3,4-trisubstituted aromatics as the core and carbohydrates as the surface group; these dendrimers were promising for application in drug delivery and as light treatment materials [26]. Recently, Malinga-Drozd [27] et al transformed G2 and G3 PAMAM into N-(2,3-dihydroxy) propyl derivatives by adding purified enantiomers R-and S-glycidyl. The obtained PAMAM-based chiral dendrimers were incubated with HaCaT and scc-15 cells.…”

Exploring the Potential of Lapatinib, Fulvestrant, and Paclitaxel Conjugated with Glycidylated PAMAM G4 Dendrimers for Cancer and Parasite Treatment

“…As a result, cancer cell drug uptake and drug resistance occur [52]. In order to eliminate the toxicity of PAMAM dendrimers and increase their permeability, their amino surface groups are hydroxylated with PEG or glycidol [53,54].…”