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      Recent progress and perspectives of continuous in vivo testing device

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          Abstract

          Devices for continuous in-vivo testing (CIVT) can detect target substances in real time, thus providing a valuable window into a patient's condition, their response to therapeutics, metabolic activities, and neurotransmitter transmission in the brain. Therefore, CIVT devices have received increased attention because they are expected to greatly assist disease diagnosis and treatment and research on human pathogenesis. However, CIVT has been achieved for only a few markers, and it remains challenging to detect many key markers. Therefore, it is important to summarize the key technologies and methodologies of CIVT, and to examine the direction of future development of CIVT. We review recent progress in the development of CIVT devices, with consideration of the structure of these devices, principles governing continuous detection, and nanomaterials used for electrode modification. This detailed and comprehensive review of CIVT devices serves three purposes: (1) to summarize the advantages and disadvantages of existing devices, (2) to provide a reference for development of CIVT equipment to detect additional important markers, and (3) to discuss future prospects with emphasis on problems that must be overcome for further development of CIVT equipment. This review aims to promote progress in research on CIVT devices and contribute to future innovation in personalized medical treatments.

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          Highlights

          • A detailed and comprehensive review of continuous in vivo testing device.

          • The nanomaterials, delicate structures and detection principles of the works are discussed.

          • The achievements and shortcomings of the existing devices are summarized.

          • The problems that should be solved in the further development of the devices and the future prospects are put forward.

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          Most cited references81

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          Aptamers as therapeutics

          Key Points Aptamers are single-stranded oligonucleotides that fold into defined architectures and bind to targets such as proteins. In binding proteins they often inhibit protein–protein interactions and thereby may elicit therapeutic effects such as antagonism. Aptamers are discovered using SELEX (systematic evolution of ligands by exponential enrichment), a directed in vitro evolution technique in which large libraries of degenerate oligonucleotides are iteratively and alternately partitioned for target binding. They are then amplified enzymatically until functional sequences are identified by the sequencing of cloned individuals. For most therapeutic purposes, aptamers are truncated to reduce synthesis costs, modified at the sugars and capped at their termini to increase nuclease resistance, and conjugated to polyethylene glycol or another entity to reduce renal filtration rates. The first aptamer approved for a therapeutic application was pegaptanib sodium (Macugen; Pfizer/Eyetech), which was approved in 2004 by the US Food and Drug Administration for macular degeneration. Eight other aptamers are currently undergoing clinical evaluation for various haematology, oncology, ocular and inflammatory indications. Aptamers are ultimately chemically synthesized in a readily scalable process in which specific conjugation points are introduced with defined stereochemistry. Unlike some protein therapeutics, aptamers do not elicit antibodies, and because aptamers generally contain sugars modified at their 2′-positions, Toll-like receptor-mediated innate immune responses are also abrogated. As aptamers are oligonucleotides they can be readily assembled into supramolecular multi-component structures using hybridization. Owing to the fact that binding to appropriate cell-surface targets can lead to internalization, aptamers can also be used to deliver therapeutic cargoes such as small interfering RNA. Supramolecular assemblies of aptamers and delivery agents have already been demonstrated in vivo and may pave the way for further therapeutic strategies with this modality in the future.
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            Advances in oligonucleotide drug delivery

            Oligonucleotides can be used to modulate gene expression via a range of processes including RNAi, target degradation by RNase H-mediated cleavage, splicing modulation, non-coding RNA inhibition, gene activation and programmed gene editing. As such, these molecules have potential therapeutic applications for myriad indications, with several oligonucleotide drugs recently gaining approval. However, despite recent technological advances, achieving efficient oligonucleotide delivery, particularly to extrahepatic tissues, remains a major translational limitation. Here, we provide an overview of oligonucleotide-based drug platforms, focusing on key approaches — including chemical modification, bioconjugation and the use of nanocarriers — which aim to address the delivery challenge.
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              Aptamers as targeted therapeutics: current potential and challenges

              Nucleic acid aptamers offer several advantages over traditional antibodies, but their clinical translation has been delayed by several factors, including insufficient potency, lack of safety data and high production costs. Here, Zhou and Rossi provide an overview of aptamer generation, focusing on recent technological advances and clinical development, as well as challenges and lessons learned.
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                Author and article information

                Contributors
                Journal
                Mater Today Bio
                Mater Today Bio
                Materials Today Bio
                Elsevier
                2590-0064
                08 July 2022
                December 2022
                08 July 2022
                : 16
                : 100341
                Affiliations
                [a ]Aerospace Information Research Institute, Chinese Academy of Sciences, Beijing, 100094, PR China
                [b ]School of Electronic, Electrical and Communication Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China
                [c ]Obstetrics and Gynecology Department, Peking University First Hospital, Beijing, 100034, PR China
                Author notes
                []Corresponding author. Aerospace Information Research Institute, Chinese Academy of Sciences, Beijing, 100094, PR China. xxcai@ 123456mail.ie.ac.cn
                [∗∗ ]Corresponding author. maggijhy@ 123456163.com
                Article
                S2590-0064(22)00139-9 100341
                10.1016/j.mtbio.2022.100341
                9305619
                35875195
                cc542b7f-e1d8-4b20-8a50-2ec6afb44244
                © 2022 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 12 April 2022
                : 22 June 2022
                : 23 June 2022
                Categories
                Review Article

                nanomaterial,in-vivo testing,microfluidic chip,continuous detection equipment,aptamer

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