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      International Journal of Nanomedicine (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Sign up for email alerts here.

      105,621 Monthly downloads/views I 7.033 Impact Factor I 10.9 CiteScore I 1.22 Source Normalized Impact per Paper (SNIP) I 1.032 Scimago Journal & Country Rank (SJR)

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      A Carrier-Free Folate Receptor-Targeted Ursolic Acid/Methotrexate Nanodelivery System for Synergetic Anticancer Therapy

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          Abstract

          Purpose

          To avoid undefined metabolic mechanisms and to eliminate potential side effects of traditional nanocarriers, new green carriers are urgently needed in cancer treatment. Carrier-free nanoparticles (NPs) based on ursolic acid (UA) have attracted significant attention, but the UA NPs targeting the folate receptor have never been explored. We designed a novel self-assembled UA-Methotrexate (MTX) NPs targeting the folate-receptor and its synergetic anticancer activity was studied in vitro and in vivo.

          Methods

          UA-MTX NPs were prepared using the solvent precipitation method. Characterization of the UA-MTX NPs preparation was performed using a size analyzer, transmission electron microscopy, and UV-vis spectrophotometry. The in vitro pH-responsive drug release capability of UA-MTX NPs was tested at different pH values. The UA-MTX NPs targeting of folates was determined by comparing the endocytosis rates of cell lines with low or overexpression of the folate receptor (A549 and MCF-7 cells). The cytotoxicity and cell apoptosis of UA-MTX NPs were also studied to determine the in vitro synergistic effects. Combination chemotherapy of UA-MTX NPs in vivo was evaluated using MCF-7 xenografted tumor models.

          Results

          Compared with free UA or MTX, the water solubility of UA-MTX NPs improved significantly. Drug-release from the UA-MTX NPs was faster at pH 5.0 than pH 7.4, suggesting MTX-UA NPs could rapidly release MTX in the acidic conditions of the tumor microenvironment. Confocal laser scanning microscopy revealed the excellent folate receptor targeting of UA-MTX NPs in MCF-7 cells. Cytotoxicity and cell apoptosis results demonstrated greater antiproliferative capacity of UA-MTX NPs than that of free drug in folate receptor overexpressing MCF-7 cells. Anticancer effects in vivo suggested MTX-UA NPs exhibited good biological safety and could enhance antitumor efficacy due to the combination therapy.

          Conclusion

          Our findings indicate that the UA-MTX NPs targeting folate-receptors is an efficient strategy for combination chemotherapy.

          Most cited references29

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          Global patterns of cancer incidence and mortality rates and trends.

          Ahmedin Jemal, Melissa M Center, Carol DeSantis … (2010)
          While incidence and mortality rates for most cancers (including lung, colorectum, female breast, and prostate) are decreasing in the United States and many other western countries, they are increasing in several less developed and economically transitioning countries because of adoption of unhealthy western lifestyles such as smoking and physical inactivity and consumption of calorie-dense food. Indeed, the rates for lung and colon cancers in a few of these countries have already surpassed those in the United States and other western countries. Most developing countries also continue to be disproportionately affected by cancers related to infectious agents, such as cervix, liver, and stomach cancers. The proportion of new cancer cases diagnosed in less developed countries is projected to increase from about 56% of the world total in 2008 to more than 60% in 2030 because of the increasing trends in cancer rates and expected increases in life expectancy and growth of the population. In this review, we describe these changing global incidence and mortality patterns for select common cancers and the opportunities for cancer prevention in developing countries. (c)2010 AACR.
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            Preventing and Managing Toxicities of High-Dose Methotrexate

            Scott C. Howard, John McCormick, Ching-hon Pui … (2016)
            High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m2, is used to treat a range of adult and childhood cancers. Although HDMTX is safely administered to most patients, it can cause significant toxicity, including acute kidney injury. This article provides comprehensive recommendations for prevention of toxicity from HDMTX, along with detailed treatment guidance to mitigate acute kidney injury and subsequent toxicity.
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              Nanocarriers for cancer-targeted drug delivery.

              Preeti Kumari, Balaram Ghosh, Swati Biswas (2016)
              Nanoparticles as drug delivery system have received much attention in recent years, especially for cancer treatment. In addition to improving the pharmacokinetics of the loaded poorly soluble hydrophobic drugs by solubilizing them in the hydrophobic compartments, nanoparticles allowed cancer specific drug delivery by inherent passive targeting phenomena and adopted active targeting strategies. For this reason, nanoparticles-drug formulations are capable of enhancing the safety, pharmacokinetic profiles and bioavailability of the administered drugs leading to improved therapeutic efficacy compared to conventional therapy. The focus of this review is to provide an overview of various nanoparticle formulations in both research and clinical applications with a focus on various chemotherapeutic drug delivery systems for the treatment of cancer. The use of various nanoparticles, including liposomes, polymeric nanoparticles, dendrimers, magnetic and other inorganic nanoparticles for targeted drug delivery in cancer is detailed.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Nanomedicine
                Journal ID (iso-abbrev): Int J Nanomedicine
                Journal ID (publisher-id): ijn
                Journal ID (pmc): intjnano
                Title: International Journal of Nanomedicine
                Publisher: Dove
                ISSN (Print): 1176-9114
                ISSN (Electronic): 1178-2013
                Publication date (Electronic): 03 March 2021
                Publication date Collection: 2021
                Volume: 16
                Pages: 1775-1787
                Affiliations
                [1 ]Experiment Center of Teaching and Learning, Shanghai University of Traditional Chinese Medicine , Shanghai, 201203, People’s Republic of China
                [2 ]School of Pharmacy, Shanghai University of Traditional Chinese Medicine , Shanghai, 201203, People’s Republic of China
                [3 ]Science and Technology Experimental Center, Shanghai University of Traditional Chinese Medicine , Shanghai, 201203, People’s Republic of China
                [4 ]Department of Pharmaceutics, University of Washington , Seattle, WA, 98195, USA
                Author notes
                Correspondence: Tong Zhang; Yue Ding Experiment Centre of Teaching and Learning, Shanghai University of Traditional Chinese Medicine , 1200 Cailun Road, Pudong New District, Shanghai, 201203, People’s Republic of ChinaTel +86 21 5132 2318; Tel +86 21 5132 2325 Email zhangtongshutcm@hotmail.com; dingyue1640@shutcm.edu.cn
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0002-2442-8613
                Article
                Publisher ID: 287806
                DOI: 10.2147/IJN.S287806
                PMC ID: 7938229
                PubMed ID: 33692622
                SO-VID: bc8c7573-ea8a-4c69-a74a-59ad92b8b694
                Copyright © © 2021 Lan et al.
                License:

                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).

                History
                Date received : 29 October 2020
                Date accepted : 22 January 2021
                Page count
                Figures: 6, Tables: 1, References: 29, Pages: 13
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Molecular medicine
                Keywords: ursolic acid,methotrexate,anticancer,carrier free,targeted drug delivery
                Data availability:
                ScienceOpen disciplines: Molecular medicine
                Keywords: ursolic acid, methotrexate, anticancer, carrier free, targeted drug delivery

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