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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.

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      Ultrastructural localization of intravenously injected carbon nanohorns in tumor

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          Abstract

          Nanocarbons have many potential medical applications. Drug delivery, diagnostic imaging, and photohyperthermia therapy, especially in the treatment of tumors, have attracted interest. For the further advancement of these application studies, the microscopic localization of nanocarbons in tumor tissues and cells is a prerequisite. In this study, carbon nanohorns (CNHs) with sizes of about 100 nm were intravenously injected into mice having subcutaneously transplanted tumors, and the CNHs in tumor tissue were observed with optical and electron microscopy. In the tumor tissue, the CNHs were found in macrophages and endothelial cells within the blood vessels. Few CNHs were found in tumor cells or in the region away from blood vessels, suggesting that, under these study conditions, the enhanced permeability of tumor blood vessels was not effective for the movement of CNHs through the vessel walls. The CNHs in normal skin tissue were similarly observed. The extravasation of CNHs was not so obvious in tumor but was easily found in normal skin, which was probably due to their vessel wall structure difference. Proper understanding of the location of CNHs in tissues is helpful in the development of the medical uses of CNHs.

          Most cited references24

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          A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs.

          We previously found that a polymer conjugated to the anticancer protein neocarzinostatin, named smancs, accumulated more in tumor tissues than did neocarzinostatin. To determine the general mechanism of this tumoritropic accumulation of smancs and other proteins, we used radioactive (51Cr-labeled) proteins of various molecular sizes (Mr 12,000 to 160,000) and other properties. In addition, we used dye-complexed serum albumin to visualize the accumulation in tumors of tumor-bearing mice. Many proteins progressively accumulated in the tumor tissues of these mice, and a ratio of the protein concentration in the tumor to that in the blood of 5 was obtained within 19 to 72 h. A large protein like immunoglobulin G required a longer time to reach this value of 5. The protein concentration ratio in the tumor to that in the blood of neither 1 nor 5 was achieved with neocarzinostatin, a representative of a small protein (Mr 12,000) in all time. We speculate that the tumoritropic accumulation of these proteins resulted because of the hypervasculature, an enhanced permeability to even macromolecules, and little recovery through either blood vessels or lymphatic vessels. This accumulation of macromolecules in the tumor was also found after i.v. injection of an albumin-dye complex (Mr 69,000), as well as after injection into normal and tumor tissues. The complex was retained only by tumor tissue for prolonged periods. There was little lymphatic recovery of macromolecules from tumor tissue. The present finding is of potential value in macromolecular tumor therapeutics and diagnosis.
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            Drug delivery with carbon nanotubes for in vivo cancer treatment.

            Chemically functionalized single-walled carbon nanotubes (SWNT) have shown promise in tumor-targeted accumulation in mice and exhibit biocompatibility, excretion, and little toxicity. Here, we show in vivo SWNT drug delivery for tumor suppression in mice. We conjugate paclitaxel (PTX), a widely used cancer chemotherapy drug, to branched polyethylene glycol chains on SWNTs via a cleavable ester bond to obtain a water-soluble SWNT-PTX conjugate. SWNT-PTX affords higher efficacy in suppressing tumor growth than clinical Taxol in a murine 4T1 breast cancer model, owing to prolonged blood circulation and 10-fold higher tumor PTX uptake by SWNT delivery likely through enhanced permeability and retention. Drug molecules carried into the reticuloendothelial system are released from SWNTs and excreted via biliary pathway without causing obvious toxic effects to normal organs. Thus, nanotube drug delivery is promising for high treatment efficacy and minimum side effects for future cancer therapy with low drug doses.
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              Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers.

              Carbon nanotubes (CNT) are intensively being developed for biomedical applications including drug and gene delivery. Although all possible clinical applications will require compatibility of CNT with the biological milieu, their in vivo capabilities and limitations have not yet been explored. In this work, water-soluble, single-walled CNT (SWNT) have been functionalized with the chelating molecule diethylentriaminepentaacetic (DTPA) and labeled with indium ((111)In) for imaging purposes. Intravenous (i.v.) administration of these functionalized SWNT (f-SWNT) followed by radioactivity tracing using gamma scintigraphy indicated that f-SWNT are not retained in any of the reticuloendothelial system organs (liver or spleen) and are rapidly cleared from systemic blood circulation through the renal excretion route. The observed rapid blood clearance and half-life (3 h) of f-SWNT has major implications for all potential clinical uses of CNT. Moreover, urine excretion studies using both f-SWNT and functionalized multiwalled CNT followed by electron microscopy analysis of urine samples revealed that both types of nanotubes were excreted as intact nanotubes. This work describes the pharmacokinetic parameters of i.v. administered functionalized CNT relevant for various therapeutic and diagnostic applications.
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                Author and article information

                Journal
                Int J Nanomedicine
                Int J Nanomedicine
                International Journal of Nanomedicine
                International Journal of Nanomedicine
                Dove Medical Press
                1176-9114
                1178-2013
                2014
                23 July 2014
                : 9
                : 3499-3508
                Affiliations
                [1 ]Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
                [2 ]Smart Energy Research Laboratories, NEC Corporation, Tsukuba, Japan
                [3 ]Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan
                [4 ]Teikyo University School of Medicine, Tokyo, Japan
                [5 ]Faculty of Science and Technology, Meijo University, Tenpaku, Nagoya, Japan
                [6 ]Nanotube Research Center, National Institute of Advanced Industrial Science and Technology, Higashi, Tsukuba, Japan
                Author notes
                Correspondence: Kiyotaka Shiba, Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan, Tel +81 335 700 489, Fax +81 335 700 461, Email kshiba@ 123456jfcr.or.jp
                Masako Yudasaka, Nanotube Research Center, National Institute of Advanced Industrial Science and Technology, 1-1-1 Higashi, Tsukuba, 305-8565, Japan, Tel +81 29 861 4818, Fax +81 29 861 6290, Email m-yudasaka@ 123456aist.go.jp
                Article
                ijn-9-3499
                10.2147/IJN.S62688
                4114911
                25092979
                7165c20d-6fa2-4efe-850b-11d5c1cdd2e7
                © 2014 Matsumura et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Molecular medicine
                ultrastructural localization,carbon nanohorn,tumor,in vivo,extravasation
                Molecular medicine
                ultrastructural localization, carbon nanohorn, tumor, in vivo, extravasation

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