Abstract
Three different amyloid targeting ligands, previously shown to exhibit amyloid specific properties, have been used to develop amyloid -targeted nanoliposomes (AT-NLs). For this a MAb against Aβ-peptides (Aβ-MAb) (immobilized on NLs at 0.015 and 0.05 mol %), and two different curcumin-lipid derivatives were attached to the surface of preformed NLs or incorporated in NL membranes during their formation. Following physicochemical characterization, these AT-NLs were studied for their ability to inhibit or delay amyloid peptide aggregation –using the thioflavin-T assay, and for their potential to reverse amyloid-induced (and Zn, or, amyloid + Zn) cytotoxicity, on wild type (N2aWT) and transformed (N2aAPP) neuroblastoma cells, applying the MTT assay. Experimental results reveal that all formulations were found to strongly delay amyloid peptide aggregation (with no significant differences between the different AT-NL types). However, although Aβ-MAb-NLs significantly reversed amyloid-induced cytotoxicity in all cases, both curcumin-NL types did not reverse Zn-induced, nor Zn+Aβ-induced cytotoxicity in N2aWT cells, suggesting lower activity against synthetic-Aβ peptides (compared to endogenous Aβ peptides); perhaps due to different affinity towards different (aggregation stages of) peptide species (monomers, oligomers, fibrils, etc). Taken into account that the aggregation stage of amyloid species is an important determinant of their toxicity, the importance of the affinity of each AT-NL type towards specific species, is highlighted.
Keywords: Alzheimer’s disease, Amyloid, Aggregation, Curcumin, Liposomes, Monoclonal Antibody, Nanoparticle, Targeting.
Current Topics in Medicinal Chemistry
Title:Comparison of Various Types of Ligand Decorated Nanoliposomes for their Ability to Inhibit Amyloid Aggregation and to Reverse Amyloid Cytotoxicity
Volume: 15 Issue: 22
Author(s): Eleni Markoutsa, Spyridon Mourtas, Erika Bereczki, Cristiano Zona, Barbara La Ferla, Fransesco Nicotra, Orfeu Flores, Jin-Jing Pei and Sophia G. Antimisiaris
Affiliation:
Keywords: Alzheimer’s disease, Amyloid, Aggregation, Curcumin, Liposomes, Monoclonal Antibody, Nanoparticle, Targeting.
Abstract: Three different amyloid targeting ligands, previously shown to exhibit amyloid specific properties, have been used to develop amyloid -targeted nanoliposomes (AT-NLs). For this a MAb against Aβ-peptides (Aβ-MAb) (immobilized on NLs at 0.015 and 0.05 mol %), and two different curcumin-lipid derivatives were attached to the surface of preformed NLs or incorporated in NL membranes during their formation. Following physicochemical characterization, these AT-NLs were studied for their ability to inhibit or delay amyloid peptide aggregation –using the thioflavin-T assay, and for their potential to reverse amyloid-induced (and Zn, or, amyloid + Zn) cytotoxicity, on wild type (N2aWT) and transformed (N2aAPP) neuroblastoma cells, applying the MTT assay. Experimental results reveal that all formulations were found to strongly delay amyloid peptide aggregation (with no significant differences between the different AT-NL types). However, although Aβ-MAb-NLs significantly reversed amyloid-induced cytotoxicity in all cases, both curcumin-NL types did not reverse Zn-induced, nor Zn+Aβ-induced cytotoxicity in N2aWT cells, suggesting lower activity against synthetic-Aβ peptides (compared to endogenous Aβ peptides); perhaps due to different affinity towards different (aggregation stages of) peptide species (monomers, oligomers, fibrils, etc). Taken into account that the aggregation stage of amyloid species is an important determinant of their toxicity, the importance of the affinity of each AT-NL type towards specific species, is highlighted.
Export Options
About this article
Cite this article as:
Markoutsa Eleni, Mourtas Spyridon, Bereczki Erika, Zona Cristiano, Ferla La Barbara, Nicotra Fransesco, Flores Orfeu, Pei Jin-Jing and Antimisiaris G. Sophia, Comparison of Various Types of Ligand Decorated Nanoliposomes for their Ability to Inhibit Amyloid Aggregation and to Reverse Amyloid Cytotoxicity, Current Topics in Medicinal Chemistry 2015; 15 (22) . https://dx.doi.org/10.2174/1568026615666150605115902
DOI https://dx.doi.org/10.2174/1568026615666150605115902 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Emerging Roles of MicroRNA-22 in Human Disease and Normal Physiology
Current Molecular Medicine PET and SPECT Radiotracers to Assess Function and Expression of ABC Transporters In Vivo
Current Drug Metabolism Properties and Pathogenicity of Prion-Derived Peptides
Protein & Peptide Letters The Role of Stem Cells in Muscular Dystrophies
Current Gene Therapy Gender Hormones: Role in the Pathogenesis of Central Nervous System Disease and Demyelination
Current Neurovascular Research <i>Uncaria tomentosa</i> (Willd. ex Schult.): Focus on Nutraceutical Aspects
Current Bioactive Compounds Nitric Oxide Synthases and Their Natural Inhibitors
Current Enzyme Inhibition Unmasking the Many Faces of Giloy (<i>Tinospora cordifolia</i> L.): A Fresh Look on its Phytochemical and Medicinal Properties
Current Pharmaceutical Design Nutritional Antioxidants and Adaptive Cell Responses: An Update
Current Molecular Medicine Monoclonal Antibodies in the Treatment of Neuroimmunological Diseases
Current Pharmaceutical Design Effects of Maternal Choline Supplementation on the Septohippocampal Cholinergic System in the Ts65Dn Mouse Model of Down Syndrome
Current Alzheimer Research Brain Innate Immunity in the Regulation of Neuroinflammation: Therapeutic Strategies by Modulating CD200-CD200R Interaction Involve the Cannabinoid System
Current Pharmaceutical Design Imaging Drug Resistance with Radiolabeled Molecules
Current Pharmaceutical Design Adenoviral Vector-Mediated Gene Transfer for Human Gene Therapy
Current Gene Therapy Senescence of the Brain: Focus on Cognitive Kinases
Current Pharmaceutical Design Mitochondrial Drug Targets in Cell Death and Cancer
Current Pharmaceutical Design Influence of the Bystander Effect on HSV-tk / GCV Gene Therapy. A Review.
Current Gene Therapy Lentiviral Vectors: A Versatile Tool to Fight Cancer
Current Molecular Medicine Synthetic 2-Methoxyestradiol Derivatives: Structure-Activity Relationships
Current Medicinal Chemistry Aptamers as Targeting Delivery Devices or Anti-cancer Drugs for Fighting Tumors
Current Drug Metabolism