Oligonucleotides carrying nucleoside antimetabolites as potential prodrugs

2021 ◽  
Vol 28 ◽  
Author(s):  
Carme Fàbrega ◽  
Anna Clua ◽  
Ramon Eritja ◽  
Anna Aviñó
Keyword(s):  
Antisense Oligonucleotides ◽  
Biomedical Applications ◽  
Enzymatic Degradation ◽  
Research Effort ◽  
Synergetic Effect ◽  
Chemotherapeutic Agents ◽  
Dna Nanostructures ◽  
Chemically Modified ◽  
Near Future ◽  
Large Research

Background: Nucleoside and nucleobase antimetabolites are an important class of chemotherapeutic agents for the treatment of cancer as well as other diseases. Introduction: In order to avoid undesirable side effects, several prodrug strategies have been developed for that purpose. In the present review, we describe a relatively unknown strategy that consists in the use of oligonucleotides modified with nucleoside antimetabolites as prodrugs. Method: The active nucleotides are generated by enzymatic degradation once incorporated into cells. This strategy has attracted large interest and is very active at present due to the continuous developments made on therapeutic oligonucleotides and the recent advances in the field of nanomaterials and nanomedicine. Results: A large research effort was done mainly in the improvement of the antiproliferative properties of nucleoside homopolymers, but recently, chemically modified aptamers, antisense oligonucleotides and/or siRNA carrying antiproliferative nucleotides have demonstrated a great potential due to the synergetic effect of both therapeutic entities. In addition, DNA nanostructures with interesting properties have been built to combine antimetabolites and enhancers of cellular uptake in the same scaffold. Finally, protein nanoparticles functionalized with receptor-binders and antiproliferative oligomers represent a new avenue for a more effective treatment in cancer therapy. Conclusion: It is expected that oligonucleotides carrying nucleoside antimetabolites will be considered as potential drugs in the near future for biomedical applications.

scholarly journals Bacterial Nanocellulose in Dentistry: Perspectives and Challenges

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 49
Author(s):  
Hélida Gomes de Oliveira Barud ◽  
Robson Rosa da Silva ◽  
Marco Antonio Costa Borges ◽  
Guillermo Raul Castro ◽  
Sidney José Lima Ribeiro ◽  
...  
Keyword(s):  
Tissue Repair ◽  
Biomedical Applications ◽  
Low Cost ◽  
Pulp Tissue ◽  
Bacterial Nanocellulose ◽  
Artificial Blood ◽  
Current Trends ◽  
Artificial Blood Vessels ◽  
Near Future ◽  
Dressing Materials

Bacterial cellulose (BC) is a natural polymer that has fascinating attributes, such as biocompatibility, low cost, and ease of processing, being considered a very interesting biomaterial due to its options for moldability and combination. Thus, BC-based compounds (for example, BC/collagen, BC/gelatin, BC/fibroin, BC/chitosan, etc.) have improved properties and/or functionality, allowing for various biomedical applications, such as artificial blood vessels and microvessels, artificial skin, and wounds dressing among others. Despite the wide applicability in biomedicine and tissue engineering, there is a lack of updated scientific reports on applications related to dentistry, since BC has great potential for this. It has been used mainly in the regeneration of periodontal tissue, surgical dressings, intraoral wounds, and also in the regeneration of pulp tissue. This review describes the properties and advantages of some BC studies focused on dental and oral applications, including the design of implants, scaffolds, and wound-dressing materials, as well as carriers for drug delivery in dentistry. Aligned to the current trends and biotechnology evolutions, BC-based nanocomposites offer a great field to be explored and other novel features can be expected in relation to oral and bone tissue repair in the near future.

N-Acetyl Galactosamine Targeting: Paving the Way for Clinical Application of Nucleotide Medicines in Cardiovascular Diseases

2021 ◽  
Author(s):  
Erik A.L. Biessen ◽  
Theo J.C. Van Berkel
Keyword(s):  
Immune Responses ◽  
Targeted Delivery ◽  
Antisense Oligonucleotides ◽  
Sugar Metabolism ◽  
Innate Immune ◽  
Future Research ◽  
Clinical Use ◽  
Innate Immune Responses ◽  
Chemically Modified ◽  
Intrinsic Capacity

While the promise of oligonucleotide therapeutics, such as (chemically modified) ASO (antisense oligonucleotides) and short interfering RNAs, is undisputed from their introduction onwards, their unfavorable pharmacokinetics and intrinsic capacity to mobilize innate immune responses, were limiting widespread clinical use. However, these major setbacks have been tackled by breakthroughs in chemistry, stability and delivery. When aiming an intervention hepatic targets, such as lipid and sugar metabolism, coagulation, not to mention cancer and virus infection, introduction of N-acetylgalactosamine aided targeting technology has advanced the field profoundly and by now a dozen of N-acetylgalactosamine therapeutics for these indications have been approved for clinical use or have progressed to clinical trial stage 2 to 3 testing. This technology, in combination with major advances in oligonucleotide stability allows safe and durable intervention in targets that were previously deemed undruggable, such as Lp(a) and PCSK9, at high efficacy and specificity, often with as little as 2 doses per year. Their successful use even the most visionary would not have predicted 2 decades ago. Here, we will review the evolution of N-acetylgalactosamine technology. We shall outline their fundamental design principles and merits, and their application for the delivery of oligonucleotide therapeutics to the liver. Finally, we will discuss the perspectives of N-acetylgalactosamine technology and propose directions for future research in receptor targeted delivery of these gene medicines.

scholarly journals Overview of DNA Self-Assembling: Progresses in Biomedical Applications

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 268 ◽  
Author(s):  
Andreia Jorge ◽  
Ramon Eritja
Keyword(s):  
Programming Languages ◽  
Biomedical Applications ◽  
Great Promise ◽  
Dna Nanostructures ◽  
Modular Assembly ◽  
Molecular Programming ◽  
Self Assembling ◽  
Theranostic Agents ◽  
Assembly Principles

Molecular self-assembling is ubiquitous in nature providing structural and functional machinery for the cells. In recent decades, material science has been inspired by the nature’s assembly principles to create artificially higher-order structures customized with therapeutic and targeting molecules, organic and inorganic fluorescent probes that have opened new perspectives for biomedical applications. Among these novel man-made materials, DNA nanostructures hold great promise for the modular assembly of biocompatible molecules at the nanoscale of multiple shapes and sizes, designed via molecular programming languages. Herein, we summarize the recent advances made in the designing of DNA nanostructures with special emphasis on their application in biomedical research as imaging and diagnostic platforms, drug, gene, and protein vehicles, as well as theranostic agents that are meant to operate in-cell and in-vivo.

Exosomal miRNA diagnostic and gene therapy tools

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Antisense Oligonucleotides ◽  
Chemotherapeutic Agents ◽  
Cancer Diagnostics ◽  
Target Delivery ◽  
Regulatory Processes ◽  
Clinical Strategies ◽  
Number Of Genes ◽  
Cancer Types ◽  
Exosomal Mirna ◽  
Generation Sequencing

The field of miRNA-based therapies is constantly expanding as a result of substantial research conducted across the world. Exosomal origin must be addressed for the use of exosomal miRNA in cancer diagnostics. A uniform procedure for exosome separation and detection should be devised, as current approaches have various limitations. More research on maximizing the benefits of target variety while avoiding off-target impacts is needed. miRNAs are involved in a number of cancer-related pathways, as well as developmental and regulatory processes. miRNAs control a large number of genes. The possibility of miRNA treatments having an off-target impact is a serious worry. Various techniques, including viral, nonviral, and chemical alterations, are recommended to improve target delivery. Nanoparticle-based delivery is being studied extensively, and attempts are being made to reduce toxicity and cellular accumulation. Next-generation sequencing of miRNAs is being used to study the functions that miRNA can play as a biomarker for diagnosis, detection, and prognosis. Several miRNA signatures unique to cancer types have evolved, with some of them now being tested in therapeutic studies. Antisense oligonucleotides that block miRNIs, tumor and CSC-targeted nanoparticle treatment, and combination treatment with chemotherapeutic agents are all promising clinical strategies for cancer personalized medicine.

scholarly journals An Ion Source for the HVEE 14C Isotope Ratio Mass Spectrometer for Biomedical Applications

Radiocarbon ◽  
1997 ◽  
Vol 40 (1) ◽  
pp. 283-288 ◽  
Author(s):  
Dirk J. W. Mous ◽  
Wim Fokker ◽  
Rein Van Den Broek ◽  
Ron Koopmans ◽  
Christopher Bronk Ramsey ◽  
...  
Keyword(s):  
Biomedical Research ◽  
Biomedical Applications ◽  
Ion Source ◽  
User Friendliness ◽  
The Past ◽  
Widespread Acceptance ◽  
First Results ◽  
Order Of Magnitude ◽  
Isotope Ratio Mass Spectrometer ◽  
Near Future

During the past two decades, accelerator mass spectrometry (AMS) has allowed major developments in many areas of geosciences and archaeology. In the near future, AMS should realize a similar potential in the field of biomedical research, leading ultimately to clinical applications. For such applications, the required instrument differs significantly from that presently used in the field of 14C dating. Whereas the needed accuracy and sensitivity is more than an order of magnitude less demanding than that for present state-of-the-art 14C instrumentation, the widespread acceptance of 14C AMS in biomedical research will require AMS spectrometers that are small, simple to operate and capable of handling CO2 samples. In order to satisfy these demands, HVEE has developed a compact 14C AMS spectrometer dedicated to biomedical research. The instrument consists of a compact accelerator with a footprint of 2.25 × 1.25 m and an ion source that features direct CO2 acceptance and optimal user friendliness. Having previously described the layout and design of the accelerator, we here discuss progress on the accelerator and present the design and first results of the CO2 ion source.

scholarly journals DLP 3D Printing Meets Lignocellulosic Biopolymers: Carboxymethyl Cellulose Inks for 3D Biocompatible Hydrogels

Polymers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 1655 ◽  
Author(s):  
Giuseppe Melilli ◽  
Irene Carmagnola ◽  
Chiara Tonda-Turo ◽  
Fabrizio Pirri ◽  
Gianluca Ciardelli ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Additive Manufacturing ◽  
3D Printing ◽  
Carboxymethyl Cellulose ◽  
Biomedical Applications ◽  
Digital Light Processing ◽  
Chemically Modified ◽  
Significant Step ◽  
3D Printed ◽  
Biomedical Field

The development of new bio-based inks is a stringent request for the expansion of additive manufacturing towards the development of 3D-printed biocompatible hydrogels. Herein, methacrylated carboxymethyl cellulose (M-CMC) is investigated as a bio-based photocurable ink for digital light processing (DLP) 3D printing. CMC is chemically modified using methacrylic anhydride. Successful methacrylation is confirmed by 1H NMR and FTIR spectroscopy. Aqueous formulations based on M-CMC/lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) photoinitiator and M-CMC/Dulbecco’s Modified Eagle Medium (DMEM)/LAP show high photoreactivity upon UV irradiation as confirmed by photorheology and FTIR. The same formulations can be easily 3D-printed through a DLP apparatus to produce 3D shaped hydrogels with excellent swelling ability and mechanical properties. Envisaging the application of the hydrogels in the biomedical field, cytotoxicity is also evaluated. The light-induced printing of cellulose-based hydrogels represents a significant step forward in the production of new DLP inks suitable for biomedical applications.

Degradation Control of Collagen by Epigallocatechin-3-O-Gallate

2007 ◽  
Vol 342-343 ◽  
pp. 781-784 ◽  
Author(s):  
Han Hee Cho ◽  
Kazuaki Matsumura ◽  
Naoki Nakajima ◽  
Dong Wook Han ◽  
Sadami Tsutsumi ◽  
...  
Keyword(s):  
Biomedical Applications ◽  
Enzymatic Degradation ◽  
Egcg Treatment ◽  
Fibrous Protein ◽  
Gel Fraction ◽  
Tissue Culture Plate ◽  
Enzymatic Degradability ◽  
The Stability ◽  
Proliferation Assays

Stabilization of the fibrous protein collagen is important in biomedical applications. This study investigated the efficacy of degradation control of collagen using (-)-epigallocatechin-3-Ogallate (EGCG). EGCG treatment of collagen in solid state was carried out and collagen sponges produced were characterized by measuring the physicochemical properties such as gel fraction, the enzymatic degradability and cytocompatibility. According to gel fraction, EGCG-treated sponges showed the increase of insolubility compared to intact sponges. It showed that EGCG played a role in a crosslinker of collagen. Through in vitro enzymatic degradation test, EGCG-treated collagen sponges showed significant enhancement of resistance to collagenase in comparison with 25 mM EDC-treated collagen sponges. Also, cell proliferation assays showed that 40 mM EGCG-treated collagen sponges exhibited similar cytocompatibility properties compared with tissue culture plate. In summary, EGCG treatment of collagen sponges increased the stability of collagen. Therefore, crosslinking of collagen based scaffold with EGCG imparted more desirable properties, making it more applicable for use as a scaffold in tissue engineering applications.

Estimating Land Surface Energy Budgets From Space: Review and Current Efforts at the University of Wisconsin—Madison and USDA–ARS

2004 ◽  
Vol 85 (1) ◽  
pp. 65-78 ◽  
Author(s):  
George R. Diak ◽  
John R. Mecikalski ◽  
Martha C. Anderson ◽  
John M. Norman ◽  
William P. Kustas ◽  
...  
Keyword(s):  
Surface Energy ◽  
Land Surface ◽  
Research Effort ◽  
Surface Fluxes ◽  
Integrated System ◽  
Energy Budgets ◽  
University Of Wisconsin ◽  
The University ◽  
Meteorological Satellite ◽  
Large Research

Since the advent of the meteorological satellite, a large research effort within the community of earth scientists has been directed at assessing the components of the land surface energy balance from space. The development of these techniques from first efforts to the present time are reviewed, and the integrated system used to estimate the radiative and turbulent land surface fluxes is described. This system is now running in real time over the continental United States at a resolution of 10 km, producing daily and time-integrated flux components.

scholarly journals Phosphorothioate modified oligonucleotide–protein interactions

2020 ◽  
Vol 48 (10) ◽  
pp. 5235-5253 ◽  
Author(s):  
Stanley T Crooke ◽  
Timothy A Vickers ◽  
Xue-hai Liang
Keyword(s):  
Protein Interactions ◽  
Antisense Oligonucleotides ◽  
Intracellular Trafficking ◽  
Recent Progress ◽  
Therapeutic Index ◽  
Pharmacological Properties ◽  
Detailed Understanding ◽  
Chemically Modified ◽  
Structure Activity ◽  
Modified Oligonucleotide

Abstract Antisense oligonucleotides (ASOs) interact with target RNAs via hybridization to modulate gene expression through different mechanisms. ASO therapeutics are chemically modified and include phosphorothioate (PS) backbone modifications and different ribose and base modifications to improve pharmacological properties. Modified PS ASOs display better binding affinity to the target RNAs and increased binding to proteins. Moreover, PS ASO protein interactions can affect many aspects of their performance, including distribution and tissue delivery, cellular uptake, intracellular trafficking, potency and toxicity. In this review, we summarize recent progress in understanding PS ASO protein interactions, highlighting the proteins with which PS ASOs interact, the influence of PS ASO protein interactions on ASO performance, and the structure activity relationships of PS ASO modification and protein interactions. A detailed understanding of these interactions can aid in the design of safer and more potent ASO drugs, as illustrated by recent findings that altering ASO chemical modifications dramatically improves therapeutic index.

Progress in Molecularly Imprinted Polymers for Biomedical Applications

2019 ◽  
Vol 22 (2) ◽  
pp. 78-88 ◽  
Author(s):  
Jane Ru Choi ◽  
Kar Wey Yong ◽  
Jean Yu Choi ◽  
Alistair C. Cowie
Keyword(s):  
Molecularly Imprinted Polymers ◽  
Biomedical Applications ◽  
Cell Imaging ◽  
Review Article ◽  
Future Perspectives ◽  
Molecularly Imprinted ◽  
Imprinted Polymers ◽  
Target Analytes ◽  
Methods Of Synthesis ◽  
Near Future

Background: Molecularly Imprinted Polymers (MIPs), a type of biomimetic materials have attracted considerable interest owing to their cost-effectiveness, good physiochemical stability, favorable specificity and selectivity for target analytes, and long shelf life. These materials are able to mimic natural recognition entities, including biological receptors and antibodies, providing a versatile platform to achieve the desirable functionality for various biomedical applications. Objective: In this review article, we introduce the most recent development of MIPs to date. We first highlight the advantages of using MIPs for a broad range of biomedical applications. We then review their various methods of synthesis along with their latest progress in biomedical applications, including biosensing, drug delivery, cell imaging and drug discovery. Lastly, the existing challenges and future perspectives of MIPs for biomedical applications are briefly discussed. Conclusion: We envision that MIPs may be used as potential materials for diverse biomedical applications in the near future.

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