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      Multicomponent, Tumor-Homing Chitosan Nanoparticles for Cancer Imaging and Therapy

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          Abstract

          Current clinical methods for cancer diagnosis and therapy have limitations, although survival periods are increasing as medical technologies develop. In most cancer cases, patient survival is closely related to cancer stage. Late-stage cancer after metastasis is very challenging to cure because current surgical removal of cancer is not precise enough and significantly affects bystander normal tissues. Moreover, the subsequent chemotherapy and radiation therapy affect not only malignant tumors, but also healthy tissues. Nanotechnologies for cancer treatment have the clear objective of solving these issues. Nanoparticles have been developed to more accurately differentiate early-stage malignant tumors and to treat only the tumors while dramatically minimizing side effects. In this review, we focus on recent chitosan-based nanoparticles developed with the goal of accurate cancer imaging and effective treatment. Regarding imaging applications, we review optical and magnetic resonance cancer imaging in particular. Regarding cancer treatments, we review various therapeutic methods that use chitosan-based nanoparticles, including chemo-, gene, photothermal, photodynamic and magnetic therapies.

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          Most cited references73

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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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            Polymer conjugates as anticancer nanomedicines.

            The transfer of polymer-protein conjugates into routine clinical use, and the clinical development of polymer-anticancer-drug conjugates, both as single agents and as components of combination therapy, is establishing polymer therapeutics as one of the first classes of anticancer nanomedicines. There is growing optimism that ever more sophisticated polymer-based vectors will be a significant addition to the armoury currently used for cancer therapy.
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              The case for early detection.

              Early detection represents one of the most promising approaches to reducing the growing cancer burden. It already has a key role in the management of cervical and breast cancer, and is likely to become more important in the control of colorectal, prostate and lung cancer. Early-detection research has recently been revitalized by the advent of novel molecular technologies that can identify cellular changes at the level of the genome or proteome, but how can we harness these new technologies to develop effective and practical screening tests?
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                08 March 2017
                March 2017
                : 18
                : 3
                : 594
                Affiliations
                [1 ]Department of Biomedical Engineering, Yonsei University, 1 Yonseidae-gil, Wonju 26493, Gangwon-do, Korea
                [2 ]Department of Systems Biotechnology, Chung-Ang University, Anseong 17546, Gyeonggi-do, Korea
                Author notes
                [* ]Correspondence: jkey@ 123456yonsei.ac.kr (J.K.); kspark1223@ 123456cau.ac.kr (K.P.); Tel.: +82-33-760-2857 (J.K.); +82-31-670-3357 (K.P.)
                Article
                ijms-18-00594
                10.3390/ijms18030594
                5372610
                28282891
                a7a89155-2616-43eb-97b3-69a16a343c04
                © 2017 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 ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 10 January 2017
                : 06 March 2017
                Categories
                Review

                Molecular biology
                chitosan,nanoparticles,drug delivery,optical imaging,magnetic resonance imaging,chemotherapy,gene therapy,photothermal therapy,photodynamic therapy,hyperthermic therapy

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