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      A Biocompatible Reconstituted High-Density Lipoprotein Nano-System as a Probe for Lung Cancer Detection

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          Abstract

          Background

          Early detection of cancer is critical and is expected to contribute significantly to the success of cancer therapy and improvement of patient survival rates.

          Material/Methods

          A biocompatible, reconstituted, high-density lipoprotein (rHDL)-based nano-system containing calcium carbonate and near-infrared fluorescence dye (NIRF), methylene blue (MB), was fabricated and characterized by particle size, zeta potential, and morphology observation. The safety profile was confirmed by bovine serum albumin (BSA) challenge assay, hemolysis test, MTT assay, and in vivo long-term toxicity assay. The tumor targetability was assessed by cellular uptake, competitive inhibition experiments, and in vivo imaging assay.

          Results

          The self-assembled rHDL/MB/CCPs exhibited desirable and homogenous particle size, neutral surface charges, high bovine serum albumin stability, low hemolytic activity, and negligible cytotoxicity in vitro. The results obtained from confocal scanning laser microscopy and flow cytometry indicated that SR-BI coating exerted tumor-targeting function, which induced high and specific cellular uptake of rHDL/MB/CCPs. In vivo investigation in an A549 tumor xenografts-bearing mouse model revealed that rHDL/MB/CCPs possessed strong tumor targetability.

          Conclusions

          rHDL/MB/CCPs could be a safe tumor-targeting probe for cancer detection.

          Related collections

          Most cited references13

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          Cancer statistics, 2000.

          The Surveillance Research Program of the American Cancer Society's Department of Epidemiology and Surveillance Research reports its annual compilation of estimated cancer incidence, mortality, and survival data for the United States in the year 2000. After 70 years of increases, the recorded number of total cancer deaths among men in the US declined for the first time from 1996 to 1997. This decrease in overall male mortality is the result of recent down-turns in lung and bronchus cancer deaths, prostate cancer deaths, and colon and rectum cancer deaths. Despite decreasing numbers of deaths from female breast cancer and colon and rectum cancer, mortality associated with lung and bronchus cancer among women continues to increase. Lung cancer is expected to account for 25% of all female cancer deaths in 2000. This report also includes a summary of global cancer mortality rates using data from the World Health Organization.
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            Calcium phosphate nanoparticles with an asymmetric lipid bilayer coating for siRNA delivery to the tumor.

            Calcium phosphate (CaP) nanoparticles (NP) with an asymmetric lipid bilayer coating have been designed for targeted delivery of siRNA to the tumor. An anionic lipid, dioleoylphosphatydic acid (DOPA), was employed as the inner leaflet lipid to coat the nano-size CaP cores, which entrap the siRNA, such that the coated cores were soluble in organic solvent. A suitable neutral or cationic lipid was used as the outer leaflet lipid to form an asymmetric lipid bilayer structure verified by the measurement of NP zeta potential. The resulting NP was named LCP-II with a size of about 25 to 30nm in diameter and contained a hollow core as revealed by TEM imaging. PEGylation of NP was done by including a PEG-phospholipid conjugate, with or without a targeting ligand anisamide, in the outer leaflet lipid mixture. The sub-cellular distribution studied in the sigma receptor positive human H460 lung cancer cells indicated that LCP-II could release more cargo to the cytoplasm than our previous lipid/protamine/DNA (LPD) formulation, leading to a significant (~40 fold in vitro and ~4 fold in vivo) improvement in siRNA delivery. Bio-distribution study showed that LCP-II required more PEGylation for MPS evasion than the previous LPD, probably due to increased surface curvature in LCP-II. Copyright © 2011 Elsevier B.V. All rights reserved.
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              Drug-incorporating calcium carbonate nanoparticles for a new delivery system.

              We devised a simple method for incorporating drugs into solid calcium carbonate nanoparticles (nano-CaCO3). The size of nano-CaCO3 was controlled by mixing speed. Washing the nanoparticles released little incorporated drug but much drug that was adsorbed on the surface. In an in vitro releasing test, granulocyte colony-stimulating factor incorporated in nano-CaCO3 was chemically stable and released very slowly. Subcutaneous injection of nano-CaCO3 incorporating betamethasone phosphate (BP) resulted in a smaller initial increase in plasma concentration and a subsequent sustained release in compared with betamethasone phosphate solution. Nano-CaCO3 may be useful to deliver hydrophilic drugs and bioactive proteins.
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                Author and article information

                Journal
                Med Sci Monit
                Med. Sci. Monit
                Medical Science Monitor
                Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
                International Scientific Literature, Inc.
                1234-1010
                1643-3750
                2015
                14 September 2015
                : 21
                : 2726-2733
                Affiliations
                [1 ]Department of Anaesthesiology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, P.R. China
                [2 ]Department of Stomatology, Qilu Hospital, Shandong University, Jinan, Shandong, P.R. China
                [3 ]Department of Stomatology, College of Physics, Shandong University, Jinan, Shandong, P.R. China
                [4 ]Department of Pulmonary Medicine, Qilu Hospital, Shandong University, Jinan, Shandong, P.R. China
                Author notes
                Corresponding Author: Dedong Ma, e-mail: mdedong@ 123456163.com
                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                Article
                895255
                10.12659/MSM.895255
                4576920
                26365043
                85e49011-c896-49fe-bca7-af9be85d7dbb
                © Med Sci Monit, 2015

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License

                History
                : 07 July 2015
                : 21 August 2015
                Categories
                Animal Study

                early detection of cancer,high-density lipoproteins, pre-beta,lung neoplasms

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