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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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      Is Open Access

      In vivo Targeting of Liver Cancer with Tissue- and Nuclei-Specific Mesoporous Silica Nanoparticle-Based Nanocarriers in mice

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          Abstract

          Purpose

          Cancer tissue-specific and nuclei-targeted drug delivery is ideal for the delivery of chemotherapy. However, it has only been achieved in in vitro studies mainly due to low efficiency in vivo. In this study, we aimed to establish an efficient dual-targeted system that targets liver cancer tissue as well as the nuclei of cancer cells in vivo.

          Methods

          We first synthesized TAT peptide (TATp)-mesoporous silica nanoparticle (MSN) complex (TATp-MSN) and generated liposomes that carried liver cancer-specific aptamer TLS11a (TLS11a-LB). We then generated the drug TLS11a-LB@TATp-MSN/doxorubicin (DOX) by mixing TLS11a-LB and DOX-loaded TATp-MSN. After physical and chemical characterization of the nanoparticles, DOX release from these formulations was evaluated at pH 5.0 and 7.4. Furthermore, we also evaluated nuclear localization and cytotoxicity of the drug in H22 cells in vitro and investigated the liver cancer targeting and antitumor activities of the nano-drug in vivo using a H22 tumor-bearing mice model.

          Results

          TLS11a-LB@TATp-MSN/DOX and its controls were confirmed as nano-drugs (<100 nm) using transmission electron microscopy (TEM). The DOX release rate of TLS11a-LB@TATp-MSN/DOX was significantly faster at pH 5.0 than at pH 7.4. TLS11a-LB@TATp-MSN/DOX effectively targeted the nuclei of H22 cells and released DOX with a higher efficiency than that of the control groups. In addition, TLS11a-LB@TATp-MSN/DOX exhibited slight cytotoxicity, but not significantly more than controls. In vivo studies showed that TLS11a-LB@TATp-MSN accumulated in subcutaneous H22 tumors in the right axilla of BALB/c mice, reaching peak levels at 48 h after intravenous injection, respectively, and demonstrated that TLS11a-LB@TATp-MSN/DOX group enhanced tumor treatment efficacy while reducing systemic side effects.

          Conclusion

          TLS11a-LB@TATp-MSN/DOX can efficiently deliver DOX to the nuclei of liver cancer cells by dual targeting liver cancer tissue and the nuclei of the cancer cells in mice. Thus, it is a promising nano-drug for the treatment of liver cancer.

          Most cited references62

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          Ahmedin Jemal, Lindsey A Torre, Rebecca Siegel … (2018)
          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            Aptamers as targeted therapeutics: current potential and challenges

            Jiehua Zhou, John M. Rossi (2016)
            Nucleic acid aptamers offer several advantages over traditional antibodies, but their clinical translation has been delayed by several factors, including insufficient potency, lack of safety data and high production costs. Here, Zhou and Rossi provide an overview of aptamer generation, focusing on recent technological advances and clinical development, as well as challenges and lessons learned.
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              Tumour stem cells and drug resistance.

              Michael Dean, Tito Fojo, Susan Bates (2005)
              The contribution of tumorigenic stem cells to haematopoietic cancers has been established for some time, and cells possessing stem-cell properties have been described in several solid tumours. Although chemotherapy kills most cells in a tumour, it is believed to leave tumour stem cells behind, which might be an important mechanism of resistance. For example, the ATP-binding cassette (ABC) drug transporters have been shown to protect cancer stem cells from chemotherapeutic agents. Gaining a better insight into the mechanisms of stem-cell resistance to chemotherapy might therefore lead to new therapeutic targets and better anticancer strategies.
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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): 29 October 2020
                Publication date Collection: 2020
                Volume: 15
                Pages: 8383-8400
                Affiliations
                [1 ]National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Medical University , Nanning, Guangxi 530021, People’s Republic of China
                [2 ]International Nanobody Research Center of Guangxi, Guangxi Medical University , Nanning, Guangxi 530021, People’s Republic of China
                [3 ]School of Preclinical Medicine, Guangxi Medical University , Nanning, Guangxi 530021, People’s Republic of China
                [4 ]College of Stomatology, Guangxi Medical University , Nanning, Guangxi 530021, People’s Republic of China
                Author notes
                Correspondence: Xiaoling Lu International Nanobody Research Center of Guangxi, Guangxi Medical University , Nanning, Guangxi530021, People’s Republic of ChinaTel/Fax +86 771-2387 518 Email luxiaoling@gxmu.edu.cn
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0003-0368-1887
                Article
                Publisher ID: 272495
                DOI: 10.2147/IJN.S272495
                PMC ID: 7605659
                PubMed ID: 33149582
                SO-VID: 4c546de2-d374-4bee-b8e0-4bfb3d7f456e
                Copyright © © 2020 Ding 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 : 21 July 2020
                Date accepted : 30 September 2020
                Page count
                Figures: 9, References: 62, Pages: 18
                Funding
                Funded by: Programs for Changjiang Scholars and Innovative Research Team in University;
                Funded by: National Natural Scientific Foundation of China;
                Funded by: the Project for International Nanobody Research Center of Guangxi;
                This work was supported, in part, by grants from Programs for Changjiang Scholars and Innovative Research Team in University (No. IRT1119), National Natural Scientific Foundation of China (No. 81372452), the Project for International Nanobody Research Center of Guangxi (No. GuiKe-AD17195001) and Guangxi Bagui Honor Scholars.
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Molecular medicine
                Keywords: targeted drug delivery,liver cancer treatment,msn-based vehicles,doxorubicin,tissue- and nuclei-specific targeting
                Data availability:
                ScienceOpen disciplines: Molecular medicine
                Keywords: targeted drug delivery, liver cancer treatment, msn-based vehicles, doxorubicin, tissue- and nuclei-specific targeting

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