scholarly journals The Interaction of Temozolomide with Blood Components Suggests the Potential Use of Human Serum Albumin as a Biomimetic Carrier for the Drug

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1015
Author(s):  
Marta Rubio-Camacho ◽  
José A. Encinar ◽  
María José Martínez-Tomé ◽  
Rocío Esquembre ◽  
C. Reyes Mateo
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Tumor Cells ◽  
Membrane Surface ◽  
Hydrolytic Stability ◽  
Tryptophan Residue ◽  
Blood Components ◽  
Dynamics Simulations ◽  
Potential Use

The interaction of temozolomide (TMZ) (the main chemotherapeutic agent for brain tumors) with blood components has not been studied at the molecular level to date, even though such information is essential in the design of dosage forms for optimal therapy. This work explores the binding of TMZ to human serum albumin (HSA) and alpha-1-acid glycoprotein (AGP), as well as to blood cell-mimicking membrane systems. Absorption and fluorescence experiments with model membranes indicate that TMZ does not penetrate into the lipid bilayer, but binds to the membrane surface with very low affinity. Fluorescence experiments performed with the plasma proteins suggest that in human plasma, most of the bound TMZ is attached to HSA rather than to AGP. This interaction is moderate and likely mediated by hydrogen-bonding and hydrophobic forces, which increase the hydrolytic stability of the drug. These experiments are supported by docking and molecular dynamics simulations, which reveal that TMZ is mainly inserted in the subdomain IIA of HSA, establishing π-stacking interactions with the tryptophan residue. Considering the overexpression of albumin receptors in tumor cells, our results propose that part of the administered TMZ may reach its target bound to plasma albumin and suggest that HSA-based nanocarriers are suitable candidates for designing biomimetic delivery systems that selectively transport TMZ to tumor cells.

Investigation of the Effects of Various Cyclodextrins on the Stabilisation of Human Serum Albumin by a Spectroscopic Method

2015 ◽  
Vol 68 (12) ◽  
pp. 1894 ◽  
Author(s):  
Mohsen Oftadeh ◽  
Golamreza Rezaei Behbahani ◽  
Ali Akbar Saboury ◽  
Shahnaz Rafiei
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Electrostatic Interactions ◽  
Spectroscopic Method ◽  
Phosphate Buffer Solution ◽  
Blue Shift ◽  
Titration Calorimetry ◽  
Tryptophan Residue ◽  
Buffer Solution

The binding parameters between cyclodextrins (CDs) and human serum albumin (HSA) were investigated by isothermal titration calorimetry (ITC), fluorescence quenching, and UV-vis absorption spectroscopy at 300 K in 50 mM phosphate buffer solution. Among the various CDs investigated, β-CD has the greater ability to decrease the aggregation of HSA and the results indicated that the inhibition order is γ-CD < α-CD < β-CD. The obtained heats for HSA+CDs interactions were reported and analysed in terms of the extended solvation model, which was used to reproduce the enthalpies of HSA interactions with CDs over a broad range of complex concentrations. The binding constant and thermodynamic parameters were obtained. These suggested that the binding reaction was driven by both enthalpy and entropy, and electrostatic interactions played a major role in the stabilising of HSA. The parameters and reflected the net effect of β-CD on the HSA stability at low and high cyclodextrin concentrations, respectively. The positive values for indicated that β-CD stabilises the HSA structure at low concentrations. The UV absorption intensity of theses complexes increased and a slight red shift was observed in the absorbance wavelength with increasing the CD concentration. The fluorescence intensity of HSA decreased regularly and a slight blue shift was observed for the emission wavelength with increasing CD concentration. The results indicate that the CD complex could quench the fluorescence of HSA and changes the microenvironment of the tryptophan residue.

Nitrosylated human serum albumin (SNO-HSA) induces apoptosis in tumor cells

Nitric Oxide ◽  
2010 ◽  
Vol 22 (4) ◽  
pp. 259-265 ◽  
Author(s):  
Naohisa Katayama ◽  
Keisuke Nakajou ◽  
Yu Ishima ◽  
Shotaro Ikuta ◽  
Jun-ichi Yokoe ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Tumor Cells

scholarly journals Human serum albumin nanoparticles loaded with phthalocyanine dyes for potential use in photodynamic therapy for atherosclerotic plaques

2019 ◽  
Vol 2 (2) ◽  
pp. 279-302 ◽  
Author(s):  
Subhadeep Banerjee ◽  
Jayeeta Sengupta ◽  
Ana Isabel Aljarilla ◽  
Francesca Setaro ◽  
Petri Makinen ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Contrast Agent ◽  
Human Serum ◽  
Zinc Phthalocyanine ◽  
Atherosclerotic Plaques ◽  
Albumin Nanoparticles ◽  
Vulnerable Plaques ◽  
Potential Use

Diseases caused by obstruction or rupture of vulnerable plaques in the arterial walls such as cardiovascular infarction or stroke are the leading cause of death in the world. In the present work, we developed human serum albumin nanoparticles loaded by physisorption with zinc phthalocyanine, TT1, mainly used for industrial application as near-infrared photosensitizer and compared these to HSA NPs loaded with the well-known silicone phthalocyanine (Pc4). The use of NIR light allows for better tissue penetration, while the use of nanoparticles permits high local concentrations. The particles were characterized and tested for toxicity and stability as well as for their potential use as a contrast agent and NIR photosensitizer for photodynamic therapy in cardiovascular disease. We focused on the distribution of the nanoparticles in RAW264.7 macrophage cells and atherosclerotic mice. The nanoparticles had an average size of 120 nm according to dynamic light scattering, good loading capacity for zinc phthalocyanine, and satisfying stability in 50% (v/v) fetal bovine serum for 8 hours and in an aqueous environment at 4°C for 4–6 weeks. Under light irradiation we found a high production of singlet oxygen and the products showed no dark toxicity in vitro with macrophages (the target cells in vulnerable plaques), but at a low g/mL nanoparticle concentration killed efficiently the macrophages upon LED illumination. Injection of the contrast agent in atherosclerotic mice led to a visible fluorescence signal of zinc phthalocyanine in the atherosclerotic plaque at 30 minutes and in the lungs with a fast clearance of the nanoparticles. Zinc phthalocyanine loaded human serum albumin nanoparticles present an interesting candidate for the visualization and potentially photodynamic treatment of macrophages in atherosclerotic plaques.

DENATURATION OF HUMAN SERUM ALBUMIN BY CERIUM (III) CHLORIDE

2013 ◽  
Vol 08 (01n02) ◽  
pp. 59-71
Author(s):  
G. REZAEI BEHBAHANI ◽  
M. SHALBAFAN ◽  
N. GHEIBI ◽  
L. BARZEGAR ◽  
H. REZAEI BEHBAHANI ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Conformational Changes ◽  
Tertiary Structure ◽  
Fluorescence Emission ◽  
Titration Calorimetry ◽  
Tryptophan Residue ◽  
Spectroscopic Methods ◽  
Irreversible Denaturation

Cerium (III) Chloride-induced conformational changes of human serum albumin, HSA, in phosphate buffer, 10 mM at pH 7.4 was investigated, using isothermal titration calorimetry (ITC), UV and fluorescence emission spectroscopic methods. The results indicate that CeCl3, Ce3+, induces irreversible denaturation of the HSA structure. The UV absorption intensity of HSA + Ce3+ shows a slight blueshift in the absorbance wavelength with increasing Ce3+ concentration. The fluorescence intensity was increased regularly and a slight redshift was observed in the emission wavelength. The HSA + Ce3+ complex quenches the fluorescence of HSA and changes the microenvironment of tryptophan residue. The emission intensity increases suggesting the loss of the tertiary structure of HSA. The results obtained from the ITC data are in agreement with the spectroscopic methods. The strong negative cooperativity of Ce3+ binding with HSA (Table 1) recovered from the extended solvation model, indicates that HSA has been denatured as a result of its interaction with Ce3+ ions.

Ruthenium (II) Complexes Interact with Human Serum Albumin and Induce Apoptosis of Tumor Cells

2014 ◽  
Vol 163 (1-2) ◽  
pp. 266-274 ◽  
Author(s):  
Jing Sun ◽  
Yongchao Huang ◽  
Chuping Zheng ◽  
Yanhui Zhou ◽  
Ying Liu ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Tumor Cells

Targeted photosensitizer nanoconjugates based on human serum albumin selectively kill tumor cells upon photo-irradiation

RSC Advances ◽  
2015 ◽  
Vol 5 (62) ◽  
pp. 50572-50579 ◽  
Author(s):  
Cheng-Yi Tang ◽  
Yong-hui Liao ◽  
Guo-Sheng Tan ◽  
Xiao-Ming Wang ◽  
Gui-Hua Lu ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Tumor Cells

Small and non-toxic nanoconjugates RGD–HSA–Ce6 could provide targeted and effective photodynamic therapy of tumor cells.

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