Abstract
Dendrimers are monodisperse, regular, three-dimensional and small-scale macromolecules that can be used to release substances such as drugs, markers, and genetic material into the cells. Among these substances, nucleic acids such as plasmid DNA, antisense oligonucleotides (asODN), and small-interfering RNA (siRNA) are widely used as therapeutic macromolecules for the treatment and prevention of diverse diseases. Several studies were focused on the modification of dendrimers aiming to improve their affinity for nucleic acids and their ability to release nucleic acids inside the cells. However, high-generation dendrimers have been shown to provoke leaking of cell membranes due to high surface-charge density. Thereby, despite the high potential of dendrimers, cytotoxicity still represents a problem to be solved prior to future in-vitro and in-vivo applications. Many approaches have proposed the introduction of diverse functional groups in low generation dendrimers, to reduce potential surface-charge density, without a loss in the ability to interact with nucleic acids. Another issue that should be addressed is how to modulate the affinity of dendrimers for nucleic acids at different pH values to guarantee an adequate release of the cargo in endosomal vesicles. These questions may be addressed through the aid of computational chemistry and bioinformatics tools. Therefore, the present review aims to provide a detailed review focused on the several techniques that have been developed for the study and design of dendrimers as carriers for DNA or RNA.
Conclusions: As shown in the present review, molecular dynamics simulations can contribute by studying at theoretical level dendrimer-nucleic acid complexes at different conditions, such as pH or ionic strength. Therefore, different cell conditions such as the stay at the cytoplasm and the transit towards endosomes can be addressed. The influence of different terminal groups of dendrimers to DNA/RNA binding can also be evaluated using molecular simulations and especially, by using free energy methods, which aim to determine affinity of dendrimers for nucleic acids. The development of a library of terminal groups for dendrimers may represent a significant contribution to the design of new dendrimers. In this regard, protein-DNA interactions of structure databases have been analyzed as a way to identify suitable residues that can be incorporated as terminal groups of dendrimers. In summary, computational chemistry and biology tools will aim the design of new dendrimers for different kinds of cargo molecules.Keywords: Dendrimers, nucleic acids, transfection, molecular dynamics, free energy calculations, macromolecules.
Current Pharmaceutical Design
Title:Multiscale Molecular Simulations Applied to Nucleic Acid-Dendrimer Interactions Studies
Volume: 23 Issue: 21
Author(s): Valeria Márquez-Miranda*, Ingrid Araya-Durán and Fernando Danilo González-Nilo*
Affiliation:
- Universidad Andres Bello, Center for Bioinformatics and Integrative Biology (CBIB), Facultad de Ciencias Biológicas, Av. República 239, Santiago,Chile
- Universidad Andres Bello, Center for Bioinformatics and Integrative Biology (CBIB), Facultad de Ciencias Biológicas, Av. República 239, Santiago,Chile
Keywords: Dendrimers, nucleic acids, transfection, molecular dynamics, free energy calculations, macromolecules.
Abstract: Dendrimers are monodisperse, regular, three-dimensional and small-scale macromolecules that can be used to release substances such as drugs, markers, and genetic material into the cells. Among these substances, nucleic acids such as plasmid DNA, antisense oligonucleotides (asODN), and small-interfering RNA (siRNA) are widely used as therapeutic macromolecules for the treatment and prevention of diverse diseases. Several studies were focused on the modification of dendrimers aiming to improve their affinity for nucleic acids and their ability to release nucleic acids inside the cells. However, high-generation dendrimers have been shown to provoke leaking of cell membranes due to high surface-charge density. Thereby, despite the high potential of dendrimers, cytotoxicity still represents a problem to be solved prior to future in-vitro and in-vivo applications. Many approaches have proposed the introduction of diverse functional groups in low generation dendrimers, to reduce potential surface-charge density, without a loss in the ability to interact with nucleic acids. Another issue that should be addressed is how to modulate the affinity of dendrimers for nucleic acids at different pH values to guarantee an adequate release of the cargo in endosomal vesicles. These questions may be addressed through the aid of computational chemistry and bioinformatics tools. Therefore, the present review aims to provide a detailed review focused on the several techniques that have been developed for the study and design of dendrimers as carriers for DNA or RNA.
Conclusions: As shown in the present review, molecular dynamics simulations can contribute by studying at theoretical level dendrimer-nucleic acid complexes at different conditions, such as pH or ionic strength. Therefore, different cell conditions such as the stay at the cytoplasm and the transit towards endosomes can be addressed. The influence of different terminal groups of dendrimers to DNA/RNA binding can also be evaluated using molecular simulations and especially, by using free energy methods, which aim to determine affinity of dendrimers for nucleic acids. The development of a library of terminal groups for dendrimers may represent a significant contribution to the design of new dendrimers. In this regard, protein-DNA interactions of structure databases have been analyzed as a way to identify suitable residues that can be incorporated as terminal groups of dendrimers. In summary, computational chemistry and biology tools will aim the design of new dendrimers for different kinds of cargo molecules.Export Options
About this article
Cite this article as:
Márquez-Miranda Valeria *, Araya-Durán Ingrid and González-Nilo Danilo Fernando*, Multiscale Molecular Simulations Applied to Nucleic Acid-Dendrimer Interactions Studies, Current Pharmaceutical Design 2017; 23 (21) . https://dx.doi.org/10.2174/1381612823666170306093224
DOI https://dx.doi.org/10.2174/1381612823666170306093224 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |

- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
-
Circulating Biochemical Markers of Brain Damage in Infants Complicated by Ischemia Reperfusion Injury
Cardiovascular & Hematological Agents in Medicinal Chemistry Mitogen-activated Protein Kinase Kinase 6-fusion Protein (MAP2K6-FP) Potentiates the Anti-tumor effects of Paclitaxel in Ovarian Cancer
Anti-Cancer Agents in Medicinal Chemistry New Biomarkers for Colon Cancer Diagnosis: A Review of Recent Patents
Recent Patents on Biomarkers Blending of Polyethylenimine with a Cationic Polyurethane Greatly Enhances Both DNA Delivery Efficacy and Reduces the Overall Cytotoxicity
Current Pharmaceutical Biotechnology Transposable Elements in Cancer and Other Human Diseases
Current Cancer Drug Targets COX Selectivity and Animal Models for Colon Cancer
Current Pharmaceutical Design Towards Environmental Construct Validity in Animal Models of CNS Disorders: Optimizing Translation of Preclinical Studies
CNS & Neurological Disorders - Drug Targets The Role of HTS in Drug Discovery at the University of Michigan
Combinatorial Chemistry & High Throughput Screening Targeted Regulation of PI3K/Akt/mTOR/NF-κB Signaling by Indole Compounds and their Derivatives: Mechanistic Details and Biological Implications for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Aneuploidy-Inducing Mutations in Mitotic Checkpoint Protein hMad1-Carboxi Terminal Domain Analyzed by SAR and Computational Mutagenesis
Current Proteomics Leukopenia Associated with Risperidone Treatment
Current Drug Safety Tamarix articulata (T. articulata) - An Important Halophytic Medicinal Plant with Potential Pharmacological Properties
Current Pharmaceutical Biotechnology Specialisation of the Tropomyosin Composition of Actin Filaments Provides New Potential Targets for Chemotherapy
Current Cancer Drug Targets Meet Our Co-Editor
Letters in Drug Design & Discovery Synthesis and Biological Evaluation of New Naphthoquinones Derivatives
Current Organic Synthesis The Role of STATs in Inflammation and Inflammatory Diseases
Current Pharmaceutical Design Recent Patents in Circulating Cell-Free Tumor DNA as Biomarker in Cancer
Recent Patents on Biomarkers Recent Developments in Nanoparticle Based Targeted Delivery of Chemotherapeutics
Current Bioactive Compounds Automated One-pot Radiosynthesis of [11C]S-adenosyl Methionine
Current Radiopharmaceuticals Erythropoietin: New Approaches to Improved Molecular Designs and Therapeutic Alternatives
Current Pharmaceutical Design