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      Transferrin-Decorated Niosomes with Integrated InP/ZnS Quantum Dots and Magnetic Iron Oxide Nanoparticles: Dual Targeting and Imaging of Glioma

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          Abstract

          The development of multifunctional nanoscale systems that can mediate efficient tumor targeting, together with high cellular internalization, is crucial for the diagnosis of glioma. The combination of imaging agents into one platform provides dual imaging and allows further surface modification with targeting ligands for specific glioma detection. Herein, transferrin (Tf)-decorated niosomes with integrated magnetic iron oxide nanoparticles (MIONs) and quantum dots (QDs) were formulated (PEGNIO/QDs/MIONs/Tf) for efficient imaging of glioma, supported by magnetic and active targeting. Transmission electron microscopy confirmed the complete co-encapsulation of MIONs and QDs in the niosomes. Flow cytometry analysis demonstrated enhanced cellular uptake of the niosomal formulation by glioma cells. In vitro imaging studies showed that PEGNIO/QDs/MIONs/Tf produces an obvious negative-contrast enhancement effect on glioma cells by magnetic resonance imaging (MRI) and also improved fluorescence intensity under fluorescence microscopy. This novel platform represents the first niosome-based system which combines magnetic nanoparticles and QDs, and has application potential in dual-targeted imaging of glioma.

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          Most cited references56

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          Advances of Non-Ionic Surfactant Vesicles (Niosomes) and Their Application in Drug Delivery

          Non-Ionic surfactant based vesicles, also known as niosomes, have attracted much attention in pharmaceutical fields due to their excellent behavior in encapsulating both hydrophilic and hydrophobic agents. In recent years, it has been discovered that these vesicles can improve the bioavailability of drugs, and may function as a new strategy for delivering several typical of therapeutic agents, such as chemical drugs, protein drugs and gene materials with low toxicity and desired targeting efficiency. Compared with liposomes, niosomes are much more stable during the formulation process and storage. The required pharmacokinetic properties can be achieved by optimizing components or by surface modification. This novel delivery system is also easy to prepare and scale up with low production costs. In this paper, we summarize the structure, components, formulation methods, quality control of niosome and its applications in chemical drugs, protein drugs and gene delivery.
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            Application of active targeting nanoparticle delivery system for chemotherapeutic drugs and traditional/herbal medicines in cancer therapy: a systematic review

            Patients treated with conventional cancer chemotherapy suffer from side effects of the drugs due to non-selective action of chemotherapeutic drugs to normal cells. Active targeting nanoparticles that are conjugated to targeting ligands on the surface of nanoparticles play an important role in improving drug selectivity to the cancer cell. Several chemotherapeutic drugs and traditional/herbal medicines reported for anticancer activities have been investigated for their selective delivery to cancer cells by active targeting nanoparticles. This systematic review summarizes reports on this application. Literature search was conducted through PubMed database search up to March 2017 using the terms nanoparticle, chemotherapy, traditional medicine, herbal medicine, natural medicine, natural compound, cancer treatment, and active targeting. Out of 695 published articles, 61 articles were included in the analysis based on the predefined inclusion and exclusion criteria. The targeting ligands included proteins/peptides, hyaluronic acid, folic acid, antibodies/antibody fragments, aptamer, and carbohydrates/polysaccharides. In vitro and in vivo studies suggest that active targeting nanoparticles increase selectivity in cellular uptake and/or cytotoxicity over the conventional chemotherapeutic drugs and non-targeted nanoparticle platform, particularly enhancement of drug efficacy and safety. However, clinical studies are required to confirm these findings.
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              Transferrin receptor-targeted theranostic gold nanoparticles for photosensitizer delivery in brain tumors.

              Therapeutic drug delivery across the blood-brain barrier (BBB) is not only inefficient, but also nonspecific to brain stroma. These are major limitations in the effective treatment of brain cancer. Transferrin peptide (Tfpep) targeted gold nanoparticles (Tfpep-Au NPs) loaded with the photodynamic pro-drug, Pc 4, have been designed and compared with untargeted Au NPs for delivery of the photosensitizer to brain cancer cell lines. In vitro studies of human glioma cancer lines (LN229 and U87) overexpressing the transferrin receptor (TfR) show a significant increase in cellular uptake for targeted conjugates as compared to untargeted particles. Pc 4 delivered from Tfpep-Au NPs clusters within vesicles after targeting with the Tfpep. Pc 4 continues to accumulate over a 4 hour period. Our work suggests that TfR-targeted Au NPs may have important therapeutic implications for delivering brain tumor therapies and/or providing a platform for noninvasive imaging.

                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                27 April 2021
                May 2021
                : 22
                : 9
                : 4556
                Affiliations
                [1 ]Institute for Particle Technology (iPAT), Technische Universität Braunschweig, 38104 Braunschweig, Germany; d.ag-seleci@ 123456tu-braunschweig.de (D.A.S.); v.maurer@ 123456tu-braunschweig.de (V.M.); c.porsiel@ 123456tu-braunschweig.de (J.C.P.); b.temel@ 123456tu-braunschweig.de (B.T.)
                [2 ]Center of Pharmaceutical Engineering (PVZ), Technische Universität Braunschweig, 38106 Braunschweig, Germany
                [3 ]Faculty of Science Biochemistry Department, Ege University, 35100 Izmir, Turkey; f.b.barlas@ 123456gmail.com (F.B.B.); elcinceylan5@ 123456gmail.com (E.C.); suna.timur@ 123456ege.edu.tr (S.T.)
                [4 ]Institute for Technical Chemistry, Leibniz University Hannover, 30167 Hannover, Germany; stahl@ 123456iftc.uni-hannover.de (F.S.); scheper@ 123456iftc.uni-hannover.de (T.S.)
                Author notes
                [†]

                Contributed equally to the work.

                Author information
                https://orcid.org/0000-0002-7582-1431
                https://orcid.org/0000-0001-6401-686X
                https://orcid.org/0000-0002-0591-6080
                https://orcid.org/0000-0002-7499-4947
                Article
                ijms-22-04556
                10.3390/ijms22094556
                8123697
                33925347
                ea5c6f66-8743-45b0-a82e-ccb85b4fddf3
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 24 March 2021
                : 23 April 2021
                Categories
                Article

                Molecular biology
                multifunctional niosomes,quantum dots,iron oxide nanoparticles,glioma imaging

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