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      Aptamer-functionalized liposomes for drug delivery

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          Abstract

          Among the various targeting ligands for drug delivery, aptamers have attracted much interest in recent years because of their smaller size compared to antibodies, ease of modification, and better batch-to-batch consistency. In addition, aptamers can be selected to target both known and even unknown cell surface biomarkers. For drug loading, liposomes are the most successful vehicle and many FDA-approved formulations are based on liposomes. In this paper, aptamer-functionalized liposomes for targeted drug delivery are reviewed. We begin with the description of related aptamers selection, followed by methods to conjugate aptamers to liposomes and the fate of such conjugates in vivo. Then a few examples of applications are reviewed. In addition to intravenous injection for systemic delivery and hoping to achieve accumulation at target sites, for certain applications, it is also possible to have aptamer/liposome conjugates applied directly at the target tissue such as intratumor injection and dropping on the surface of the eye by adhering to the cornea. While previous reviews have focused on cancer therapy, the current review mainly covers other applications in the last four years. Finally, this article discusses potential issues of aptamer targeting and some future research opportunities.

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          Lipid nanoparticles for mRNA delivery

          Messenger RNA (mRNA) has emerged as a new category of therapeutic agent to prevent and treat various diseases. To function in vivo, mRNA requires safe, effective and stable delivery systems that protect the nucleic acid from degradation and that allow cellular uptake and mRNA release. Lipid nanoparticles have successfully entered the clinic for the delivery of mRNA; in particular, lipid nanoparticle–mRNA vaccines are now in clinical use against coronavirus disease 2019 (COVID-19), which marks a milestone for mRNA therapeutics. In this Review, we discuss the design of lipid nanoparticles for mRNA delivery and examine physiological barriers and possible administration routes for lipid nanoparticle–mRNA systems. We then consider key points for the clinical translation of lipid nanoparticle–mRNA formulations, including good manufacturing practice, stability, storage and safety, and highlight preclinical and clinical studies of lipid nanoparticle–mRNA therapeutics for infectious diseases, cancer and genetic disorders. Finally, we give an outlook to future possibilities and remaining challenges for this promising technology. Lipid nanoparticle–mRNA formulations have entered the clinic as coronavirus disease 2019 (COVID-19) vaccines, marking an important milestone for mRNA therapeutics. This Review discusses lipid nanoparticle design for mRNA delivery, highlighting key points for clinical translation and preclinical studies of lipid nanoparticle–mRNA therapeutics for various diseases.
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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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              New Developments in Liposomal Drug Delivery.

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                Author and article information

                Contributors
                Journal
                Biomed J
                Biomed J
                Biomedical Journal
                Chang Gung University
                2319-4170
                2320-2890
                10 December 2023
                August 2024
                10 December 2023
                : 47
                : 4
                : 100685
                Affiliations
                [a ]Department of Chemistry, Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, Canada
                [b ]Centre for Eye and Vision Research (CEVR), Hong Kong
                [c ]Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hong Kong
                [d ]Research Center for Chinese Medicine Innovation, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong
                Author notes
                []Corresponding author. Department of Chemistry, Waterloo Institute for Nanotechnology, 200 University Avenue West, Waterloo, Ontario N2L 3G1, Canada. liujw@ 123456uwaterloo.ca
                Article
                S2319-4170(23)00122-1 100685
                10.1016/j.bj.2023.100685
                11340590
                38081386
                8c5fb310-96b1-447a-af38-9be5e58e6c02
                © 2023 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
                : 8 August 2023
                : 21 October 2023
                : 5 December 2023
                Categories
                Review Article

                liposomes,aptamers,targeted drug delivery,tumors,eye
                liposomes, aptamers, targeted drug delivery, tumors, eye

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