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      Formulation optimization of lyophilized aptamer-gold nanoparticles: Maintained colloidal stability and cellular uptake

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          Abstract

          Anti-nucleolin (NCL) aptamer AS1411 is the first anticancer aptamer tested in clinical trials. Gold nanoparticles (AuNP) have been widely exploited for various biomedical applications due to their unique functional properties. In this study, we evaluated the colloidal stability and targeting capacity of AS1411-funtionalized AuNP (AuNP/NCL-Apt) against MCF-7 breast cancer cell line before and after lyophilization. Trehalose, mannitol, and sucrose at various concentrations were evaluated to determine their cryoprotection effects. Our results indicate that sucrose at 10 % (w/v) exhibits the best cryoprotection effect and minimal AuNP/NCL-Apt aggregation as confirmed by UV–Vis spectroscopy and dynamic light scattering (DLS) measurements. Moreover, the lyophilized AuNP/NCL-Apt at optimized formulation maintained its targeting and cytotoxic functionality against MCF-7 cells as proven by the cellular uptake assays utilizing flow cytometry and confocal laser scanning microscopy (CLSM). Quantitative PCR (qPCR) analysis of nucleolin-target gene expression also confirmed the effectiveness of AuNP/NCL-Apt. This study highlights the importance of selecting the proper type and concentration of cryoprotectant in the typical nanoparticle lyophilization process and contributes to our understanding of the physical and biological properties of functionalized nanoparticles upon lyophilization.

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          Most cited references66

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          Engineering precision nanoparticles for drug delivery

          In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations of free therapeutics and navigate biological barriers — systemic, microenvironmental and cellular — that are heterogeneous across patient populations and diseases. Overcoming this patient heterogeneity has also been accomplished through precision therapeutics, in which personalized interventions have enhanced therapeutic efficacy. However, nanoparticle development continues to focus on optimizing delivery platforms with a one-size-fits-all solution. As lipid-based, polymeric and inorganic nanoparticles are engineered in increasingly specified ways, they can begin to be optimized for drug delivery in a more personalized manner, entering the era of precision medicine. In this Review, we discuss advanced nanoparticle designs utilized in both non-personalized and precision applications that could be applied to improve precision therapies. We focus on advances in nanoparticle design that overcome heterogeneous barriers to delivery, arguing that intelligent nanoparticle design can improve efficacy in general delivery applications while enabling tailored designs for precision applications, thereby ultimately improving patient outcome overall.
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            Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase

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              In vitro selection of RNA molecules that bind specific ligands.

              Subpopulations of RNA molecules that bind specifically to a variety of organic dyes have been isolated from a population of random sequence RNA molecules. Roughly one in 10(10) random sequence RNA molecules folds in such a way as to create a specific binding site for small ligands.
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                Author and article information

                Contributors
                Journal
                Heliyon
                Heliyon
                Heliyon
                Elsevier
                2405-8440
                08 May 2024
                30 May 2024
                08 May 2024
                : 10
                : 10
                : e30743
                Affiliations
                [a ]Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Irbid, 22110, Jordan
                [b ]Cell Therapy Center, The University of Jordan, Amman, 11942, Jordan
                [c ]Department of Nanoscience, Joint School of Nanoscience and Nanoengineering, University of North Carolina at Greensboro, 2907 E. Gate City Blvd, Greensboro, NC, 27401, USA
                [d ]Pharmacological and Diagnostic Research Center, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, 19328, Jordan
                [e ]College of Pharmacy, QU Health, Qatar University, Doha, 2713, Qatar
                Author notes
                [* ]Corresponding author. mmobeidat82@ 123456just.edu.jo
                [** ]Corresponding author. College of Pharmacy, Qatar University, Doha, 2713, Qatar. alkilany@ 123456qu.edu.qa
                [1]

                Contributes equally.

                Article
                S2405-8440(24)06774-4 e30743
                10.1016/j.heliyon.2024.e30743
                11107208
                38774322
                04146b7a-36f2-4761-ad6f-8008bbcdeab0
                © 2024 The Authors

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

                History
                : 9 January 2024
                : 1 May 2024
                : 3 May 2024
                Categories
                Research Article

                aptamer,gold nanoparticles,aggregation,cryoprotectants,lyophilization

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