Pyrazolo[3,4-d]pyrimidines-loaded human serum albumin (HSA) nanoparticles: Preparation, characterization and cytotoxicity evaluation against neuroblastoma cell line

AbstractResistance to systemic drug therapies is a major reason for the failure of anti-cancer therapies. Here, we tested doxorubicin-loaded human serum albumin (HSA) nanoparticles in the neuroblastoma cell line UKF-NB-3 and its ABCB1-expressing sublines adapted to vincristine (UKF-NB-3rVCR1) and doxorubicin (UKF-NB-3rDOX20). Doxorubicin-loaded nanoparticles displayed increased anti-cancer activity in UKF-NB-3rVCR1and UKF-NB-3rDOX20cells relative to doxorubicin solution, but not in UKF-NB-3 cells. UKF-NB-3rVCR1cells were resensitised by nanoparticle-encapsulated doxorubicin to the level of UKF-NB-3 cells. UKF-NB-3rDOX20cells displayed a more pronounced resistance phenotype than UKF-NB-3rVCR1cells and were not re-sensitised by doxorubicin-loaded nanoparticles to the level of parental cells. ABCB1 inhibition using zosuquidar resulted in similar effects like nanoparticle incorporation, indicating that doxorubicin-loaded nanoparticles circumvent ABCB1-mediated drug efflux. The limited re-sensitisation of UKF-NB-3rDOX20cells to doxorubicin by circumvention of ABCB1-mediated efflux is probably due to the presence of multiple doxorubicin resistance mechanisms. So far, ABCB1 inhibitors have failed in clinical trials, probably because systemic ABCB1 inhibition results in a modified body distribution of its many substrates including drugs, xenobiotics, and other molecules. HSA nanoparticles may provide an alternative, more specific way to overcome transporter-mediated resistance.

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Doxorubicin-loaded human serum albumin nanoparticles overcome transporter-mediated drug resistance in drug-adapted cancer cells

Beilstein Journal of Nanotechnology ◽

10.3762/bjnano.10.166 ◽

2019 ◽

Vol 10 ◽

pp. 1707-1715 ◽

Cited By ~ 14

Author(s):

Hannah Onafuye ◽

Sebastian Pieper ◽

Dennis Mulac ◽

Jindrich Cinatl Jr. ◽

Mark N Wass ◽

...

Keyword(s):

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Neuroblastoma Cell ◽

Resistance Mechanisms ◽

Neuroblastoma Cell Line ◽

Drug Efflux ◽

Albumin Nanoparticles ◽

Body Distribution ◽

Systemic Drug

Resistance to systemic drug therapy is a major reason for the failure of anticancer therapies. Here, we tested doxorubicin-loaded human serum albumin (HSA) nanoparticles in the neuroblastoma cell line UKF-NB-3 and its ABCB1-expressing sublines adapted to vincristine (UKF-NB-3rVCR1) and doxorubicin (UKF-NB-3rDOX20). Doxorubicin-loaded nanoparticles displayed increased anticancer activity in UKF-NB-3rVCR1 and UKF-NB-3rDOX20 cells relative to doxorubicin solution, but not in UKF-NB-3 cells. UKF-NB-3rVCR1 cells were re-sensitised by nanoparticle-encapsulated doxorubicin to the level of UKF-NB-3 cells. UKF-NB-3rDOX20 cells displayed a more pronounced resistance phenotype than UKF-NB-3rVCR1 cells and were not re-sensitised by doxorubicin-loaded nanoparticles to the level of parental cells. ABCB1 inhibition using zosuquidar resulted in similar effects like nanoparticle incorporation, indicating that doxorubicin-loaded nanoparticles successfully circumvent ABCB1-mediated drug efflux. The limited re-sensitisation of UKF-NB-3rDOX20 cells to doxorubicin by circumvention of ABCB1-mediated efflux is probably due to the presence of multiple doxorubicin resistance mechanisms. So far, ABCB1 inhibitors have failed in clinical trials probably because systemic ABCB1 inhibition results in a modified body distribution of its many substrates including drugs, xenobiotics, and other molecules. HSA nanoparticles may provide an alternative, more specific way to overcome transporter-mediated resistance.

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Interaction of Arylidenechromanone/Flavanone Derivatives with Biological Macromolecules Studied as Human Serum Albumin Binding, Cytotoxic Effect, Biocompatibility Towards Red Blood Cells

Molecules ◽

10.3390/molecules23123172 ◽

2018 ◽

Vol 23 (12) ◽

pp. 3172 ◽

Cited By ~ 3

Author(s):

Angelika A. Adamus-Grabicka ◽

Magdalena Markowicz-Piasecka ◽

Michał B. Ponczek ◽

Joachim Kusz ◽

Magdalena Małecka ◽

...

Keyword(s):

Human Serum Albumin ◽

Serum Albumin ◽

Red Blood Cells ◽

Human Serum ◽

Cell Line ◽

Cell Lines ◽

Blood Cells ◽

Cytotoxic Effect ◽

Human Leukemia ◽

Ic50 Values

The aim of this study was to determine the cytotoxic effect of 3-arylidenechromanone (1) and 3arylideneflavanone (2) on HL-60 and NALM-6 cell lines (two human leukemia cell lines) and a WM-115 melanoma cell line. Both compounds exhibited high cytotoxic activity with higher cytotoxicity exerted by compound 2, for which IC50 values below 10 µM were found for each cell line. For compound 1, the IC50 values were higher than 10 µM for HL-60 and WM-115 cell lines, but IC50 < 10 µM was found for the NALM-6 cell line. Both compounds, at the concentrations close to IC50 (concentration range: 5–24 µM/L for compound 1 and 6–10 µM/L for compound 2), are not toxic towards red blood cells. The synthesized compounds were characterized using spectroscopic methods 1H- and 13C-NMR, IR, MS, elemental analysis, and X-ray diffraction. The lipophilicity of both synthesized compounds was determined using an RP-TLC method and the logP values found were compared with the theoretical ones taken from the Molinspiration Cheminformatics (miLogP) software package. The mode of binding of both compounds to human serum albumin was assessed using molecular docking methods.

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Adherence of Streptococcus pneumoniae to Respiratory Epithelial Cells Is Inhibited by Sialylated Oligosaccharides

Infection and Immunity ◽

10.1128/iai.66.4.1439-1444.1998 ◽

1998 ◽

Vol 66 (4) ◽

pp. 1439-1444 ◽

Cited By ~ 69

Author(s):

Roger Barthelson ◽

Ali Mobasseri ◽

David Zopf ◽

Paul Simon

Keyword(s):

Streptococcus Pneumoniae ◽

Human Serum Albumin ◽

Epithelial Cells ◽

Serum Albumin ◽

Human Serum ◽

Cell Line ◽

Airway Epithelial Cells ◽

Logarithmic Phase ◽

Respiratory Epithelial Cells ◽

Respiratory Epithelial

ABSTRACT To study carbohydrate-mediated adherence of Streptococcus pneumoniae to the human airway, we measured binding of liveS. pneumoniae organisms to a cultured cell line derived from the lining of the conjunctiva and to primary monolayers of human bronchial epithelial cells in the presence and absence of oligosaccharide inhibitors. Both encapsulated and nonencapsulated strains of S. pneumoniae grown to mid-logarithmic phase in suspension culture adhered to cultured primary respiratory epithelial cells and the conjunctival cell line. Adherence of nine clinically prevalent S. pneumoniaecapsular types studied was inhibited preferentially by sialylated oligosaccharides that terminate with the disaccharide NeuAcα2-3(or 6)Galβ1. Adherence of some strains also was weakly inhibited by oligosaccharides that terminate with lactosamine (Galβ1-4GlcNAcβ1). When sialylated oligosaccharides were covalently coupled to human serum albumin at a density of approximately 20 oligosaccharides per molecule of protein, the molar inhibitory potency of the oligosaccharide inhibitor was enhanced 500-fold. The above-mentioned experiments reveal a previously unreported dependence upon sialylated carbohydrate ligands for adherence of S. pneumoniae to human upper airway epithelial cells. Enhanced inhibitory potencies of polyvalent over monovalent forms of oligosaccharide inhibitors of adherence suggest that the putative adhesin(s) that recognizes the structure NeuAcα2-3(or 6)Galβ1 is arranged on the bacterial surface in such a manner that it may be cross-linked by oligosaccharides covalently linked to human serum albumin.

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