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      Folic acid-modified laponite nanodisks for targeted anticancer drug delivery

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          Abstract

          Folic acid-modified laponite nanodisks can be used as an efficient platform for targeted delivery of doxorubicin via a receptor-mediated pathway.

          Abstract

          We report here an effective approach to modifying laponite (LAP) nanodisks with folic acid (FA) for targeted anticancer drug delivery applications. In this approach, LAP nanodisks were first modified with 3-aminopropyldimethylethoxysilane (APMES) to render them with abundant surface amines, followed by conjugation with FA via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) chemistry. The formed FA-modified LAP nanodisks (LM-FA) were then used to encapsulate anticancer drug doxorubicin (DOX). The surface modification of LAP nanodisks and the subsequent drug encapsulation within the LAP nanodisks were characterized via different techniques. We show that the LM-FA is able to encapsulate DOX with an efficiency of 92.1 ± 2.2%, and the formed LM-FA/DOX complexes are able to release DOX in a pH-dependent manner with a higher DOX release rate under acidic pH conditions than under physiological pH conditions. The encapsulation of DOX within LM-FA does not compromise its therapeutic activity. Importantly, the formed LM-FA/DOX complexes are able to specifically target cancer cells overexpressing high-affinity FA receptors as confirmed via flow cytometric analysis and confocal microscopic observation, and exert specific therapeutic efficacy to the target cancer cells. The developed FA-modified LAP nanodisks may hold great promise to be used as an efficient nanoplatform for targeted delivery of different anticancer drugs.

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          Nuclear-targeted drug delivery of TAT peptide-conjugated monodisperse mesoporous silica nanoparticles.

          Limin Pan, Qianjun He, Jianan Liu … (2012)
          Most present nanodrug delivery systems have been developed to target cancer cells but rarely nuclei. However, nuclear-targeted drug delivery is expected to kill cancer cells more directly and efficiently. In this work, TAT peptide has been employed to conjugate onto mesoporous silica nanoparticles (MSNs-TAT) with high payload for nuclear-targeted drug delivery for the first time. Monodispersed MSNs-TAT of varied particle sizes have been synthesized to investigate the effects of particle size and TAT conjugation on the nuclear membrane penetrability of MSNs. MSNs-TAT with a diameter of 50 nm or smaller can efficiently target the nucleus and deliver the active anticancer drug doxorubicin (DOX) into the targeted nucleus, killing these cancer cells with much enhanced efficiencies. This study may provide an effective strategy for the design and development of cell-nuclear-targeted drug delivery.
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            Differential regulation of folate receptor isoforms in normal and malignant tissues in vivo and in established cell lines. Physiologic and clinical implications.

            P. Chaudhuri, Andrew J. Ross, M Ratnam (1994)
            Despite significant differences in ligand binding between the two known isoforms of the human membrane folate receptor (FR), designated herein as FR-beta (placenta) and FR-alpha (placenta, KB cells), little is known about their tissue specificities, and there is no report on the relative expression of FR-beta in any tissue other than in placenta. The mRNA for each FR isoform in a wide variety of normal fetal and adult tissue explants, primary normal cell cultures, malignant tumor explants, and established tumor cell lines was estimated by a polymerase chain reaction assay. Total receptor levels were estimated by a [3H] folic acid binding assay. Both the FR isoforms were expressed in fetal as well as adult tissues. Normal tissues generally expressed low to moderate amounts of FR-beta. FR-alpha alone was expressed in normal epithelial cells and was frequently strikingly elevated in a variety of carcinomas, with the exception of squamous cell carcinomas of the head and neck. In contrast, a variety of malignant tissues of nonepithelial origin generally expressed elevated levels of FR-beta alone. Established tumor cell lines expressed FR-alpha virtually alone and did not reflect FR expression patterns in vivo. KB cells and JEG-3 cells grown at low folate concentrations further up-regulated FR-alpha but not FR-beta. Although FR-beta is the more common isoform, FR-alpha and FR-beta are differentially regulated in normal tissues, carcinomas, nonepithelial malignancies, and immortalized cells or in response to changes in extracellular folate concentrations. The tissue specificity of FR isoforms and their elevation in malignant tissues may be a significant factor in FR-mediated folate uptake, in tissue responsiveness to promising novel antifolates, and in FR-related immunodiagnosis/immunotherapy.
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              Targeted delivery and controlled release of doxorubicin to cancer cells using modified single wall carbon nanotubes.

              Xiaoke Zhang, Lingjie Meng, Qinghua Lu … (2009)
              A targeted drug delivery system that is triggered by changes in pH based on single wall carbon nanotubes (SWCNTs), derivatized with carboxylate groups and coated with a polysaccharide material, can be loaded with the anticancer drug doxorubicin (DOX). The drug binds at physiological pH (pH 7.4) and is only released at a lower pH, for example, lysosomal pH and the pH characteristic of certain tumor environments. By manipulating the surface potentials of the modified nanotubes through modification of the polysaccharide coating, both the loading efficiency and release rate of the associated DOX can be controlled. Folic acid (FA), a targeting agent for many tumors, can be additionally tethered to the SWCNTs to selectively deliver DOX into the lysosomes of HeLa cells with much higher efficiency than free DOX. The DOX released from the modified nanotubes has been shown to damage nuclear DNA and inhibit the cell proliferation.
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                Author and article information

                Journal
                Journal ID (publisher-id): JMCBDV
                Title: J. Mater. Chem. B
                Abbreviated Title: J. Mater. Chem. B
                Publisher: Royal Society of Chemistry (RSC)
                ISSN (Print): 2050-750X
                ISSN (Electronic): 2050-7518
                Publication date Created: 2014
                Publication date (Electronic): 2014
                Volume: 2
                Issue: 42
                Pages: 7410-7418
                Affiliations
                [1 ]College of Chemistry
                [2 ]Chemical Engineering and Biotechnology, Donghua University
                [3 ]Shanghai 201620, People's Republic of China
                [4 ]State Key Laboratory for Modification of Chemical Fibers and Polymer Materials
                [5 ]Donghua University
                [6 ]Comprehensive Breast Health Center, Renji Hospital
                [7 ]Shanghai 200127, People's Republic of China
                [8 ]Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine
                [9 ]Shanghai 200025, People's Republic of China
                Article
                DOI: 10.1039/C4TB01162G
                PubMed ID: 32261966
                SO-VID: 571b4332-f35d-41e6-9a11-1f55bde3b2f9
                Copyright © © 2014
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