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      Zinc oxide end-capped Fe 3O 4@mSiO 2 core-shell nanocarriers as targeted and responsive drug delivery system for chemo-/ions synergistic therapeutics

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          Abstract

          Multifunctional core-shell nanocarriers based on zinc oxide (ZnO)-gated magnetic mesoporous silica nanoparticles (MMSN) were prepared for cancer treatment through magnetic targeting and pH-triggered controlled drug release. Under an external magnetic field, the MMSN could actively deliver chemotherapeutic agent, daunomycin (DNM), to the targeted sites. At neutral aqueous, the functionalized MMSN could stably accommodate the DNM molecules since the mesopores were capped by the ZnO gatekeepers. In contrast, at the acid intercellular environment, the gatekeepers would be removed to control the release of drugs due to the dissolution of ZnO. Meanwhile, ZnO quantum dots not only rapidly dissolve in an acidic condition of cancer cells but also enhance the anti-cancer effect of Zn 2+. An in vitro controlled release proliferation indicated that the acid sensitive ZnO gatekeepers showed well response by the ‘on-off’ switch of the pores. Cellular experiments against cervical cancer cell (HeLa cells) further showed that functionalized MMSN significantly suppressed cancer cells growth through synergistic effects between the chemotherapy and Zn 2+ ions with monitoring the treatment process. These results suggested that the ZnO-gated MMSN platform is a promising approach to serve as a pH-sensitive system for chemotherapies delivery and Zn 2+ controlled release for further application in the treatment of various cancers by synergistic effects.

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          Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties.

          Tian Xia, Michael Kovochich, Monty Liong … (2008)
          Nanomaterials (NM) exhibit novel physicochemical properties that determine their interaction with biological substrates and processes. Three metal oxide nanoparticles that are currently being produced in high tonnage, TiO(2), ZnO, and CeO(2), were synthesized by flame spray pyrolysis process and compared in a mechanistic study to elucidate the physicochemical characteristics that determine cellular uptake, subcellular localization, and toxic effects based on a test paradigm that was originally developed for oxidative stress and cytotoxicity in RAW 264.7 and BEAS-2B cell lines. ZnO induced toxicity in both cells, leading to the generation of reactive oxygen species (ROS), oxidant injury, excitation of inflammation, and cell death. Using ICP-MS and fluorescent-labeled ZnO, it is found that ZnO dissolution could happen in culture medium and endosomes. Nondissolved ZnO nanoparticles enter caveolae in BEAS-2B but enter lysosomes in RAW 264.7 cells in which smaller particle remnants dissolve. In contrast, fluorescent-labeled CeO(2) nanoparticles were taken up intact into caveolin-1 and LAMP-1 positive endosomal compartments, respectively, in BEAS-2B and RAW 264.7 cells, without inflammation or cytotoxicity. Instead, CeO(2) suppressed ROS production and induced cellular resistance to an exogenous source of oxidative stress. Fluorescent-labeled TiO(2) was processed by the same uptake pathways as CeO(2) but did not elicit any adverse or protective effects. These results demonstrate that metal oxide nanoparticles induce a range of biological responses that vary from cytotoxic to cytoprotective and can only be properly understood by using a tiered test strategy such as we developed for oxidative stress and adapted to study other aspects of nanoparticle toxicity.
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            Functionalized mesoporous silica materials for controlled drug delivery.

            Piaoping Yang, Shili Gai, Jun Lin (2012)
            In the past decade, non-invasive and biocompatible mesoporous silica materials as efficient drug delivery systems have attracted special attention. Great progress in structure control and functionalization (magnetism and luminescence) design has been achieved for biotechnological and biomedical applications. This review highlights the most recent research progress on silica-based controlled drug delivery systems, including: (i) pure mesoporous silica sustained-release systems, (ii) magnetism and/or luminescence functionalized mesoporous silica systems which integrate targeting and tracking abilities of drug molecules, and (iii) stimuli-responsive controlled release systems which are able to respond to environmental changes, such as pH, redox potential, temperature, photoirradiation, and biomolecules. Although encouraging and potential developments have been achieved, design and mass production of novel multifunctional carriers, some practical biological application, such as biodistribution, the acute and chronic toxicities, long-term stability, circulation properties and targeting efficacy in vivo are still challenging. This journal is © The Royal Society of Chemistry 2012
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              pH-Sensitive Delivery Vehicle Based on Folic Acid-Conjugated Polydopamine-Modified Mesoporous Silica Nanoparticles for Targeted Cancer Therapy.

              Wei Cheng, Junpeng Nie, Lv Xu … (2017)
              In this study, we introduced a targeting polymer poly(ethylene glycol)-folic acid (PEG-FA) on the surface of polydopamine (PDA)-modified mesoporous silica nanoparticles (MSNs) to develop the novel nanoparticles (NPs) MSNs@PDA-PEG-FA, which were employed as a drug delivery system loaded with doxorubicin (DOX) as a model drug for cervical cancer therapy. The chemical structure and properties of these NPs were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, N2 adsorption/desorption, dynamic light scattering-autosizer, thermogravimetric analysis, and Fourier transform infrared spectroscopy. The pH-sensitive PDA coating served as a gatekeeper. The in vitro drug release experiments showed pH-dependent and sustained drug release profiles that could enhance the therapeutic anticancer effect and minimize potential damage to normal cells due to the acidic microenvironment of the tumor. These MSNs@PDA-PEG-FA achieved significantly high targeting efficiency, which was demonstrated by the in vitro cellular uptake and cellular targeting assay. Compared with that of free DOX and DOX-loaded NPs without the folic targeting ligand, the FA-targeted NPs exhibited higher antitumor efficacy in vivo, implying that they are a highly promising potential carrier for cancer treatments.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Drug Deliv
                Journal ID (iso-abbrev): Drug Deliv
                Journal ID (publisher-id): IDRD
                Journal ID (publisher-id): idrd20
                Title: Drug Delivery
                Publisher: Taylor & Francis
                ISSN (Print): 1071-7544
                ISSN (Electronic): 1521-0464
                Publication date Collection: 2019
                Publication date (Electronic): 25 July 2019
                Volume: 26
                Issue: 1
                Pages: 732-743
                Affiliations
                [a ]School of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University , Wenzhou, China;
                [b ]School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University , Guangzhou, China;
                [c ]Wenzhou Institute, University of Chinese Academy of Sciences , Wenzhou, China;
                [d ]Department of Chemical Engineering, Northeastern University , Boston, MA, USA;
                [e ]Department of Bioengineering, Northeastern University , Boston, MA, USA;
                [f ]Department of Chemistry and Chemical Biology, Northeastern University , Boston, MA, USA
                Author notes
                [*]

                These authors contributed equally to this work.

                All authors have given approval to the final version of this manuscript.

                CONTACT Ping Zhao zhaoping666@ 123456163.com School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University , Guangzhou 510006, China;
                Jianliang Shen shenjl@ 123456wibe.ac.cn School of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University , Wenzhou 325035, China
                Article
                Publisher ID: 1642419
                DOI: 10.1080/10717544.2019.1642419
                PMC ID: 6713220
                PubMed ID: 31340678
                SO-VID: b307d1e2-733a-4212-a34a-d4383298f745
                Copyright © © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 10 June 2019
                Date revision received : 04 July 2019
                Date accepted : 08 July 2019
                Page count
                Figures: 6, Tables: 0, Pages: 12, Words: 7363
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Funded by: Zhejiang Provincial Natural Science of Foundation of China
                Award ID: 01
                Funded by: Wenzhou Medical University and Wenzhou Institute of Biomaterials and Engineering
                Award ID: 001-03
                Funded by: Natural Science Foundation of Guangdong
                Award ID: 7
                This work was financially supported by the National Natural Science Foundation of China [31800833], Zhejiang Provincial Natural Science of Foundation of China [Z19H180001], the Wenzhou Medical University and Wenzhou Institute of Biomaterials and Engineering [WIBEZD2017001-03] and Natural Science Foundation of Guangdong [2016A030313807].
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: magnetic mesoporous silica nanoparticles,zno,daunomycin,ph-responsive,synergistic effects
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: magnetic mesoporous silica nanoparticles, zno, daunomycin, ph-responsive, synergistic effects

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