Biological activity of N(4)-boronated derivatives of 2′-deoxycytidine, potential agents for boron-neutron capture therapy

Nizioł, Joanna; Uram, Łukasz; Szuster, Magdalena; Sekuła, Justyna; Ruman, Tomasz

doi:10.1016/j.bmc.2015.08.026

Cited by 14 publications

(6 citation statements)

References 29 publications

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“…The cytotoxicity of 5 in human fibroblast (BJ) and glioblastoma (U‐118 MG) cells was determined using the neutral red (NR) assay as described previously . NR is a colorimetric assay to determine the degree of the membrane permeability and lysosomal activity in response to chemical or pharmaceutical compounds ,.…”

Section: Resultsmentioning

confidence: 99%

PAMAM Dendrimers Attached to Collagen via a Malondialdehyde Linker

et al. 2017

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Functionalization of polyamidoamine dendrimers (PAMAM) for use as macromolecular drug carriers with aldehydes was performed using aminoacetaldehyde dimethylacetal (AADA) and malondialdehyde (MDA). AADA was used to obtain low molecular weight product upon reaction with dimethyl succinate and PAMAM G‐0.5. The structure of succinate bis‐(dimethylacetal)acetamide was elucidated by X‐ray crystallography. This product, as well as the product of condensation of PAMAM G‐0.5 with AADA, were resistant to hydrolysis. MDA reacted with iso‐butylamine and polyamidoamine PAMAM G0 dendrimers to give 3‐[N‐(2‐methylpropyl)amino]prop‐2‐enal and PAMAM G0 with four arms ending with prop‐2‐enal groups. The compounds were characterized by NMR, MS and/or elemental analysis. PAMAM G3 was also converted to aldehyde‐terminated dendrimer with excess MDA, however, the product was water insoluble. The low molecular weight water soluble analogue prop‐2‐enal terminated PAMAM G0 dendrimer was tested for toxicity on normal human fibroblasts and glioblastoma cell cultures. The toxicity of prop‐2‐enal terminated PAMAM G0 was comparable with that of amine ending PAMAM G0. Finally, fluorescein‐labeled PAMAM G3 was covalently attached to a collagen scaffold via a MDA linker as demonstrated by confocal microcopy. This rapid method of covalent attachment of PAMAM‐drug conjugates to MDA‐activated collagen opens new pathways for delivery of drugs into tissue.

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Section: Resultsmentioning

confidence: 99%

PAMAM Dendrimers Attached to Collagen via a Malondialdehyde Linker

et al. 2017

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“…HaCaT cells (4×10 4 cells/well) were cultured and treated for 24 h with dendrimers at concentrations of 0, 5, 10 and 50 μM, similarly as for the cytotoxicity assay. The assay was performed as previously described (Nizioł et al, 2015).…”

Section: Methodsmentioning

confidence: 99%

Evaluation of the localization and biological effects of PAMAM G3 dendrimer-biotin/pyridoxal conjugate as HaCaT keratinocyte targeted nanocarrier

Szuster¹,

Uram²,

Filipowicz-Rachwał³

et al. 2019

Acta Biochim Pol

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Recognition of the molecular mechanisms of keratinocyte participation in normal skin homeostasis and in pathogenesis may lead to creation of more effective tools for topical application of cosmetics, cosmeceutics and drugs to a particular location within the skin for prevention and therapy of many skin disorders and diseases. For this purpose, the PAMAM G3 dendrimer with amide linkages of 9 biotin molecules and 10 molecules of pyridoxal phosphate (BC-PAMAM) was constructed, and its biological properties and cellular uptake and localization were investigated in the HaCaT keratinocytes. BC-PAMAM is nontoxic for HaCaT cells, as estimated by two assays (Neutral Red and tetrazolium salt reduction, XTT), and revealed low apoptosis induction at up to 50 µM concentration. Fluorescent labeled BC-PAMAM accumulates in HaCaT cells with high efficiency in a concentration–dependent manner. Its mitochondrial localization, estimated as Mander’s colocalization coefficient, is substantially lower than the native PAMAM, and that correlates with its cytotoxicity. The only undesirable, but significant inhibitory effect on cell mobility, evaluated by the wound healing test, was observed at 10 µM BC-PAMAM. The important anti-inflammatory action of BC-PAMAM was clearly documented by decreased production of total IL-1α, assayed with an ELISA test with unstimulated and stimulated by bacterial antigens (LPS and GroEL) HaCaT cells. Thus, it is expected that the biotin pyridoxal phosphate conjugated PAMAM may be considered as a potential carrier for safe delivery of vitamins and drugs into the epidermis.

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“…HaCaT and SCC-15 cells were seeded in flat-bottom 96-well culture plates in triplicate (100 µL cell suspension per well) at a density of 1 × 10 4 cells/well and allowed to attach for 24 h. The stock solution of 3 mM dendrimers was filtered with sterile syringe filters (0.22 µm) and used to treatment of cells with a range of increasing concentrations from 0 to 300 µM (100 µL/well) for 24 h in 37 • C. After that, the neutral red assay was performed as described [24].…”

Section: Toxicity Assaymentioning

confidence: 99%

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

et al. 2021

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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.

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Biological activity of N(4)-boronated derivatives of 2′-deoxycytidine, potential agents for boron-neutron capture therapy

Cited by 14 publications

References 29 publications

PAMAM Dendrimers Attached to Collagen via a Malondialdehyde Linker

PAMAM Dendrimers Attached to Collagen via a Malondialdehyde Linker

Evaluation of the localization and biological effects of PAMAM G3 dendrimer-biotin/pyridoxal conjugate as HaCaT keratinocyte targeted nanocarrier

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

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