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      Delivery Of Curcumin Nanoliposomes Using Surface Modified With CD133 Aptamers For Prostate Cancer

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          Abstract

          Aim

          The aim of this study was to characterize curcumin (CUR)-loaded CD133 aptamer A15 liposomes for their antitumor activity in vitro and in vivo.

          Methods

          The modified CUR liposomes were prepared by the thin-film hydration technique.

          Results

          The particles showed spherical shape under electron microscopy with sizes <100 nm. Initial drug burst release was observed within 2 hrs and then the drug was continuously released over 48 hrs. No aggregation or precipitation of liposomes was observed during storage for 3 months. In vitro results showed that blank LPs had lower cellular cytotoxicity. Both liposomes of CUR (with or without A15 modified) exhibited a similar trend of cellular cytotoxicity at the same concentration. With the extension of incubation time, A15-CUR LPs showed a greater inhibitory effect on cells. Cell internalization in DU145 cells was higher for A15-CUR LPs than others. An in vivo study using DU145 prostate carcinoma bearing mice showed that A15-CUR LPs reduced tumor growth more than other forms of CUR.

          Conclusion

          These results indicate that A15 modified CUR liposomes are a promising candidate for antitumor drug delivery.

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          Most cited references 29

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          Evolution of the cancer stem cell model.

          Genetic analyses have shaped much of our understanding of cancer. However, it is becoming increasingly clear that cancer cells display features of normal tissue organization, where cancer stem cells (CSCs) can drive tumor growth. Although often considered as mutually exclusive models to describe tumor heterogeneity, we propose that the genetic and CSC models of cancer can be harmonized by considering the role of genetic diversity and nongenetic influences in contributing to tumor heterogeneity. We offer an approach to integrating CSCs and cancer genetic data that will guide the field in interpreting past observations and designing future studies. Copyright © 2014 Elsevier Inc. All rights reserved.
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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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              Multiple biological activities of curcumin: a short review.

              Turmeric (Curcuma longa rhizomes), commonly used as a spice is well documented for its medicinal properties in Indian and Chinese systems of medicine. It has been widely used for the treatment of several diseases. Epidemiological observations, though inconclusive, are suggestive that turmeric consumption may reduce the risk of some form of cancers and render other protective biological effects in humans. These biological effects of turmeric have been attributed to its constituent curcumin that has been widely studied for its anti-inflammatory, anti-angiogenic, anti-oxidant, wound healing and anti-cancer effects. As a result of extensive epidemiological, clinical, and animal studies several molecular mechanisms are emerging that elucidate multiple biological effects of curcumin. This review summarizes the most interesting in vitro and in vivo studies on the biological effects of curcumin.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                DDDT
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                28 November 2019
                2019
                : 13
                : 4021-4033
                Affiliations
                [1 ]Department of Ultrasound, The Second Affiliated Hospital of Soochow University , Suzhou, People’s Republic of China
                [2 ]Department of Urology, The Second Affiliated Hospital of Soochow University , Suzhou, People’s Republic of China
                [3 ]Department of Operation, The Second Affiliated Hospital of Soochow University , Suzhou, People’s Republic of China
                Author notes
                Correspondence: Wei Tao Department of Urology, The Second Affiliated Hospital of Soochow University , No. 1055 Sanxiang Road, Gusu District, Suzhou City, Jiangsu Province, People’s Republic of ChinaTel/Fax +86 0512-67784837 Email tw27024@163.com
                Yanling Zhou Department of Operation, The Second Affiliated Hospital of Soochow University , No. 1055 Sanxiang Road, Gusu District, Suzhou City, Jiangsu Province, People’s Republic of China Email sdfeyzyl@163.com
                [*]

                These authors contributed equally to this work

                Article
                210949
                10.2147/DDDT.S210949
                6886545
                © 2019 Ma et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 9, Tables: 4, References: 32, Pages: 13
                Categories
                Original Research

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