The effect of G3 PAMAM dendrimer conjugated with B-group vitamins on cell morphology, motility and ATP level in normal and cancer cells

Uram, Łukasz; Szuster, Magdalena; Misiorek, Maria; Filipowicz, Aleksandra; Wołowiec, Stanisław; Wałajtys-Rode, Elżbieta

doi:10.1016/j.ejps.2017.03.022

Cited by 16 publications

(10 citation statements)

References 49 publications

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“…There is a variety of PAMAM terminal amine group modifications reported till now, like PEG-ylation, acylation, and hydroxyalkylation [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ], which modify not only the basicity of intrinsic nitrogen atoms but also tune surface hydrophilicity vs. hydrophobicity. On the other hand, amine groups are convenient peripheral sites to attach potential ligands like folate or biotin and are responsible for binding a conjugated carrier selectively to cancer cell membranes [ 5 , 8 , 10 , 13 , 14 , 15 , 16 , 17 , 18 ]. Conjugates bearing anticancer drugs, targeting molecules, and surface-modifying substituents may serve as selective and systematically nontoxic anticancer drugs.…”

Section: Introductionmentioning

confidence: 99%

Stepwise Glucoheptoamidation of Poly(Amidoamine) Dendrimer G3 to Tune Physicochemical Properties of the Potential Drug Carrier: In Vitro Tests for Cytisine Conjugates

et al. 2020

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Third-generation poly(amidoamine) dendrimer (PAMAM) was modified by stepwise primary amine group amidation with d-glucoheptono-1,4-lactone. The physicochemical properties of the conjugates—size, ζ potential in lysosomal pH 5 and in neutral aqueous solutions, as well as intramolecular dynamics by differential scanning calorimetry—were determined. Internalization and toxicity of the conjugates against normal human fibroblasts BJ were monitored in vitro in order to select an appropriate carrier for a drug delivery system. It was found that initial glucoheptoamidation (up to 1/3 of amine groups of neat dendrimers available) resulted in increase of conjugate size and ζ potential. Native or low substituted dendrimer conjugates accumulated efficiently in fibroblast cells at nontoxic 1 µM concentration. Further substitution of dendrimer caused consistent decrease of size and ζ potential, cell accumulation, and toxicity. All dendrimers are amorphous at 36.6 °C as determined by differential scanning calorimetry (DSC). The optimized dendrimer, half-filled with glucoheptoamide substituents, was applied as carrier bearing two covalently attached cytisine molecules: a rigid and hydrophobic alkaloid. The conjugate with 2 cytisine and 16 glucoheptoamide substituents showed fast accumulation and no toxicity up to 200 µM concentration. The half-glucoheptoamidated PAMAM dendrimer was selected as a promising anticancer drug carrier for further applications.

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Section: Introductionmentioning

confidence: 99%

Stepwise Glucoheptoamidation of Poly(Amidoamine) Dendrimer G3 to Tune Physicochemical Properties of the Potential Drug Carrier: In Vitro Tests for Cytisine Conjugates

et al. 2020

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“…Cells were cultured in 24-well plates at 2×10 5 cell/ well (24 h, 37°C) to confluence. Wound healing assay was performed as described (Uram et al, 2017).…”

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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“…For instance, dendrimer nanoparticles find useful functionalization in the following areas: i) increase biocompatibility (by PEGylating [53] or acetylation [54]); ii) enhance transfection efficiency (usually by aminoacid [55] or lipid functionalization [18]); iii) induce site specific delivery (e.g. aptamer [56], antibody [57], vitamin [58], peptides [59,60]); or iv) to render stimuli responsive dendrimer nanoparticles (e.g. pH [61], thermo [62], photo [63], redox-responsive [64]).…”

Section: Journal Of Materials Chemistry B Accepted Manuscriptmentioning

confidence: 99%

Dendrimer nanoparticles for colorectal cancer applications

2020

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The effect of G3 PAMAM dendrimer conjugated with B-group vitamins on cell morphology, motility and ATP level in normal and cancer cells

Cited by 16 publications

References 49 publications

Stepwise Glucoheptoamidation of Poly(Amidoamine) Dendrimer G3 to Tune Physicochemical Properties of the Potential Drug Carrier: In Vitro Tests for Cytisine Conjugates

Stepwise Glucoheptoamidation of Poly(Amidoamine) Dendrimer G3 to Tune Physicochemical Properties of the Potential Drug Carrier: In Vitro Tests for Cytisine Conjugates

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

Dendrimer nanoparticles for colorectal cancer applications

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