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      Anti-Epcam Aptamer (Syl3c)-Functionalized Liposome for Targeted Delivery Of Doxorubicin: In Vitro And In Vivo Antitumor Studies in Mice Bearing C26 Colon Carcinoma

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          Abstract

          In this study, we have surface-functionalized PEGylated-nanoliposomal doxorubicin (DOX) with anti-EpCAM (epithelial cell adhesion molecule) aptamer via post-insertion of anti-EpCAM aptamer-conjugated DSPE-mPEG 2000 into Caelyx® (ED-lip). The size, charge, release profile, and cytotoxicity and cellular uptake of formulation were determined. The characterization of the ED-lip demonstrated the slightly increase in size and PDI along with the decrease in zeta potential which indicated that post-insertion efficiently done. The results of flow cytometry and fluorescent microscopy have shown that ED-lip enhanced the rate of cell uptake on C26 cell line compared to Caelyx®. The ED-lip also had more cytotoxic effects than Caelyx® which indicated the efficacy of anti-EpCAM aptamer as targeting ligand. The pharmacokinetic and tissue biodistribution of formulations in mice bearing C26 tumors demonstrated that ED-lip did not affect the distribution profile of DOX compared to Caelyx® in animal model. In addition, ED-lip effectively improved the tumor accumulation of DOX and promoted survival of animals compared to Caelyx®. These results suggest that the functionalization of Caelyx® with anti-EpCAM aptamer is promising in cancer treatment and merits further investigation.

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          Analysis of nanoparticle delivery to tumours

          Stefan Wilhelm, Anthony Tavares, Huan-Qin Dai … (2016)
          Article 0 comments Cited 1286 times – based on 0 reviews     Review now
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            Progress and challenges towards targeted delivery of cancer therapeutics

            Daniel Rosenblum, Nitin Joshi, Wei Tao … (2018)
            Targeted delivery approaches for cancer therapeutics have shown a steep rise over the past few decades. However, compared to the plethora of successful pre-clinical studies, only 15 passively targeted nanocarriers (NCs) have been approved for clinical use and none of the actively targeted NCs have advanced past clinical trials. Herein, we review the principles behind targeted delivery approaches to determine potential reasons for their limited clinical translation and success. We propose criteria and considerations that must be taken into account for the development of novel actively targeted NCs. We also highlight the possible directions for the development of successful tumor targeting strategies.
            Article 0 comments Cited 601 times – based on 0 reviews     Review now
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              Aptamers as therapeutics

              Anthony Keefe, Supriya Pai, Andrew Ellington (2010)
              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.
              Article 0 comments Cited 588 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Mahmoud Reza Jaafari:
                ORCID: http://orcid.org/0000-0003-3908-6828
                jafarimr@mums.ac.ir
                Journal
                Journal ID (nlm-ta): Nanoscale Res Lett
                Journal ID (iso-abbrev): Nanoscale Res Lett
                Title: Nanoscale Research Letters
                Publisher: Springer US (New York )
                ISSN (Print): 1931-7573
                ISSN (Electronic): 1556-276X
                Publication date (Electronic): 7 May 2020
                Publication date PMC-release: 7 May 2020
                Publication date Collection: 2020
                Volume: 15
                Electronic Location Identifier: 101
                Affiliations
                [1 ]GRID grid.411583.a, ISNI 0000 0001 2198 6209, Nanotechnology Research Center, Pharmaceutical Technology Institute, , Mashhad University of Medical Sciences, ; Mashhad, Iran
                [2 ]GRID grid.411583.a, ISNI 0000 0001 2198 6209, Department of Pharmaceutical Nanotechnology, School of Pharmacy, , Mashhad University of Medical Sciences, ; Mashhad, Iran
                [3 ]GRID grid.411583.a, ISNI 0000 0001 2198 6209, Department of Medical Biotechnology, Faculty of Medicine, , Mashhad University of Medical Sciences, ; Mashhad, Iran
                [4 ]GRID grid.411583.a, ISNI 0000 0001 2198 6209, Biotechnology Research Center, Pharmaceutical Technology Institute, , Mashhad University of Medical Sciences, ; Mashhad, Iran
                Author information
                http://orcid.org/0000-0003-3908-6828
                Article
                Publisher ID: 3334
                DOI: 10.1186/s11671-020-03334-9
                PMC ID: 7206479
                PubMed ID: 32383027
                SO-VID: 4e91611c-c7c0-4633-829e-40b7fb8ce0a3
                Copyright © © The Author(s) 2020
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 23 December 2019
                Date accepted : 24 April 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100012155, National Institute for Medical Research Development;
                Award ID: 943732
                Award Recipient :
                Categories
                Subject: Nano Express
                Custom metadata
                issue-copyright-statement © The Author(s) 2020

                ScienceOpen disciplines: Nanomaterials
                Keywords: epcam,aptamer,liposomes,doxorubicin,colon cancer
                Data availability:
                ScienceOpen disciplines: Nanomaterials
                Keywords: epcam, aptamer, liposomes, doxorubicin, colon cancer

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