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      Surface Functionalization and Targeting Strategies of Liposomes in Solid Tumor Therapy: A Review

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          Abstract

          Surface functionalization of liposomes can play a key role in overcoming the current limitations of nanocarriers to treat solid tumors, i.e., biological barriers and physiological factors. The phospholipid vesicles (liposomes) containing anticancer agents produce fewer side effects than non-liposomal anticancer formulations, and can effectively target the solid tumors. This article reviews information about the strategies for targeting of liposomes to solid tumors along with the possible targets in cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature. Targeting ligands for functionalization of liposomes with relevant surface engineering techniques have been described. Stimuli strategies for enhanced delivery of anticancer agents at requisite location using stimuli-responsive functionalized liposomes have been discussed. Recent approaches for enhanced delivery of anticancer agents at tumor site with relevant surface functionalization techniques have been reviewed. Finally, current challenges of functionalized liposomes and future perspective of smart functionalized liposomes have been discussed.

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          Most cited references132

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          Current trends in the use of liposomes for tumor targeting.

          The use of liposomes for drug delivery began early in the history of pharmaceutical nanocarriers. These nanosized, lipid bilayered vesicles have become popular as drug delivery systems owing to their efficiency, biocompatibility, nonimmunogenicity, enhanced solubility of chemotherapeutic agents and their ability to encapsulate a wide array of drugs. Passive and ligand-mediated active targeting promote tumor specificity with diminished adverse off-target effects. The current field of liposomes focuses on both clinical and diagnostic applications. Recent efforts have concentrated on the development of multifunctional liposomes that target cells and cellular organelles with a single delivery system. This review discusses the recent advances in liposome research in tumor targeting.
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            Effects of nanomaterial physicochemical properties on in vivo toxicity.

            It is well recognized that physical and chemical properties of materials can alter dramatically at nanoscopic scale, and the growing use of nanotechnologies requires careful assessment of unexpected toxicities and biological interactions. However, most in vivo toxicity concerns focus primarily on pulmonary, oral, and dermal exposures to ultrafine particles. As nanomaterials expand as therapeutics and as diagnostic tools, parenteral administration of engineered nanomaterials should also be recognized as a critical aspect for toxicity consideration. Due to the complex nature of nanomaterials, conflicting studies have led to different views of their safety. Here, the physicochemical properties of four representative nanomaterials (dendrimers, carbon nanotubes, quantum dots, and gold nanoparticles) as it relates to their toxicity after systemic exposure is discussed.
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              Differentiation and reversal of malignant changes in colon cancer through PPARgamma.

              PPARgamma is a nuclear receptor that has a dominant regulatory role in differentiation of cells of the adipose lineage, and has recently been shown to be expressed in the colon. We show here that PPARgamma is expressed at high levels in both well- and poorly-differentiated adenocarcinomas, in normal colonic mucosa and in human colon cancer cell lines. Ligand activation of this receptor in colon cancer cells causes a considerable reduction in linear and clonogenic growth, increased expression of carcinoembryonic antigen and the reversal of many gene expression events specifically associated with colon cancer. Transplantable tumors derived from human colon cancer cells show a significant reduction of growth when mice are treated with troglitazone, a PPARgamma ligand. These results indicate that the growth and differentiation of colon cancer cells can be modulated through PPARgamma.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                09 January 2018
                January 2018
                : 19
                : 1
                : 195
                Affiliations
                [1 ]School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Kowloon, Hong Kong, China; kashif@ 123456life.hkbu.edu.hk (M.K.R.); zhangxueflora@ 123456163.com (X.Z.); cong_cong_lilly@ 123456126.com (C.L.); 16483081@ 123456life.hkbu.edu.hk (K.H.W.); cxyu2016@ 123456hkbu.edu.hk (X.C.); zhangge@ 123456hkbu.edu.hk (G.Z.)
                [2 ]School of Chemical and Biomolecular Engineering, The University of Sydney, Sydney, NSW 2006, Australia; mria8901@ 123456uni.sydney.edu.au
                Author notes
                Author information
                https://orcid.org/0000-0002-7807-7695
                https://orcid.org/0000-0002-6094-0438
                Article
                ijms-19-00195
                10.3390/ijms19010195
                5796144
                29315231
                03833737-30bc-44d2-b9bc-79d317d0274f
                © 2018 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
                : 06 December 2017
                : 04 January 2018
                Categories
                Review

                Molecular biology
                liposomes,targeted drug delivery,solid tumor,targeting ligands,surface functionalization

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