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      Targeted and redox-responsive drug delivery systems based on carbonic anhydrase IX-decorated mesoporous silica nanoparticles for cancer therapy

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          Abstract

          In this work, we developed a new antibody-targeted and redox-responsive drug delivery system “MSNs-CAIX” by binding the anti-carbonic anhydrase IX antibody (A-CAIX Ab) on the surface of mesoporous silica nanoparticles (MSNs) via disulfide linkages. The design of the composite particles “MSNs-CAIX” involved the synthesis and surface functionalization with thiol groups, 2,2′-dipyridyl disulfide and CAIX antibody. In vitro, CAIX capping the doxorubicin hydrochloric (DOX)-loaded nanoparticles (DOX@MSNs-CAIX) exhibited effectively redox-responsive release in the presence of glutathione (GSH) owing to the cleavage of the disulfide bond. Compared with CAIX negative Mef cells (mouse embryo fibroblast), remarkably more DOX@MSNs-CAIX was internalized into CAIX positive 4T1 cells (mouse breast cancer cells) by receptor-mediation. Tumor targeting in vivo studies clearly demonstrated DOX@MSNs-CAIX accumulated in tumors and induced more tumor cells apoptosis in 4T1 tumor-bearing mice. With great potential, this drug delivery system is a promising candidate for targeted and redox-responsive cancer therapy.

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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 633 times – based on 0 reviews     Review now
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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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              Mesoporous Silica Nanoparticles: A Comprehensive Review on Synthesis and Recent Advances

              Reema Narayan, Usha Nayak, Ashok Raichur … (2018)
              Recent advancements in drug delivery technologies utilizing a variety of carriers have resulted in a path-breaking revolution in the approach towards diagnosis and therapy alike in the current times. Need for materials with high thermal, chemical and mechanical properties have led to the development of mesoporous silica nanoparticles (MSNs). These ordered porous materials have garnered immense attention as drug carriers owing to their distinctive features over the others. They can be synthesized using a relatively simple process, thus making it cost effective. Moreover, by controlling the parameters during the synthesis; the morphology, pore size and volume and particle size can be transformed accordingly. Over the last few years, a rapid increase in research on MSNs as drug carriers for the treatment of various diseases has been observed indicating its potential benefits in drug delivery. Their widespread application for the loading of small molecules as well as macromolecules such as proteins, siRNA and so forth, has made it a versatile carrier. In the recent times, researchers have sorted to several modifications in the framework of MSNs to explore its potential in drug resistant chemotherapy, antimicrobial therapy. In this review, we have discussed the synthesis of these multitalented nanoparticles and the factors influencing the size and morphology of this wonder carrier. The second part of this review emphasizes on the applications and the advances made in the MSNs to broaden the spectrum of its use especially in the field of biomedicine. We have also touched upon the lacunae in the thorough understanding of its interaction with a biological system which poses a major hurdle in the passage of this carrier to the clinical level. In the final part of this review, we have discussed some of the major patents filed in the field of MSNs for therapeutic purpose.
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                Author and article information

                Contributors
                Xichuan Cao: xichuancao@cumt.edu.cn
                Zhuoqi Zhang: zhuoqizhang@sina.com
                Journal
                Journal ID (nlm-ta): Sci Rep
                Journal ID (iso-abbrev): Sci Rep
                Title: Scientific Reports
                Publisher: Nature Publishing Group UK (London )
                ISSN (Electronic): 2045-2322
                Publication date (Electronic): 2 September 2020
                Publication date PMC-release: 2 September 2020
                Publication date Collection: 2020
                Volume: 10
                Electronic Location Identifier: 14447
                Affiliations
                [1 ]GRID grid.411510.0, ISNI 0000 0000 9030 231X, School of Materials and Physics, , China University of Mining and Technology, ; Xuzhou, 221116 People’s Republic of China
                [2 ]GRID grid.411510.0, ISNI 0000 0000 9030 231X, School of Chemical Engineering and Technology, , China University of Mining and Technology, ; Xuzhou, 221116 People’s Republic of China
                [3 ]GRID grid.413389.4, Department of Cardiology, , Affiliated Hospital of Xuzhou Medical University, ; Xuzhou, 221002 People’s Republic of China
                [4 ]GRID grid.417303.2, ISNI 0000 0000 9927 0537, Cancer Institute, Xuzhou Medical University, ; Xuzhou, 221002 People’s Republic of China
                Article
                Publisher ID: 71071
                DOI: 10.1038/s41598-020-71071-1
                PMC ID: 7467921
                PubMed ID: 32879359
                SO-VID: 382eaf8d-9eea-4e73-854c-8ce693d2ecc2
                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 : 26 December 2019
                Date accepted : 6 August 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: No.3 0670557
                Award ID: No. 30800219
                Funded by: Natural Science Foundation of JiangSu Province P.R. China
                Award ID: No. BK2008132
                Categories
                Subject: Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2020

                ScienceOpen disciplines: Uncategorized
                Keywords: cancer therapy,biomedical materials,drug delivery,nanoparticles
                Data availability:
                ScienceOpen disciplines: Uncategorized
                Keywords: cancer therapy, biomedical materials, drug delivery, nanoparticles

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