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      Advanced Nanobiomaterials: Vaccines, Diagnosis and Treatment of Infectious Diseases

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          Abstract

          The use of nanoparticles has contributed to many advances due to their important properties such as, size, shape or biocompatibility. The use of nanotechnology in medicine has great potential, especially in medical microbiology. Promising data show the possibility of shaping immune responses and fighting severe infections using synthetic materials. Different studies have suggested that the addition of synthetic nanoparticles in vaccines and immunotherapy will have a great impact on public health. On the other hand, antibiotic resistance is one of the major concerns worldwide; a recent report of the World Health Organization (WHO) states that antibiotic resistance could cause 300 million deaths by 2050. Nanomedicine offers an innovative tool for combating the high rates of resistance that we are fighting nowadays, by the development of both alternative therapeutic and prophylaxis approaches and also novel diagnosis methods. Early detection of infectious diseases is the key to a successful treatment and the new developed applications based on nanotechnology offer an increased sensibility and efficiency of the diagnosis. The aim of this review is to reveal and discuss the main advances made on the science of nanomaterials for the prevention, diagnosis and treatment of infectious diseases. Highlighting innovative approaches utilized to: (i) increasing the efficiency of vaccines; (ii) obtaining shuttle systems that require lower antibiotic concentrations; (iii) developing coating devices that inhibit microbial colonization and biofilm formation.

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          A DNA-based method for rationally assembling nanoparticles into macroscopic materials.

          C Mirkin, R Letsinger, R Mucic … (1996)
          Colloidal particles of metals and semiconductors have potentially useful optical, optoelectronic and material properties that derive from their small (nanoscopic) size. These properties might lead to applications including chemical sensors, spectroscopic enhancers, quantum dot and nanostructure fabrication, and microimaging methods. A great deal of control can now be exercised over the chemical composition, size and polydispersity of colloidal particles, and many methods have been developed for assembling them into useful aggregates and materials. Here we describe a method for assembling colloidal gold nanoparticles rationally and reversibly into macroscopic aggregates. The method involves attaching to the surfaces of two batches of 13-nm gold particles non-complementary DNA oligonucleotides capped with thiol groups, which bind to gold. When we add to the solution an oligonucleotide duplex with 'sticky ends' that are complementary to the two grafted sequences, the nanoparticles self-assemble into aggregates. This assembly process can be reversed by thermal denaturation. This strategy should now make it possible to tailor the optical, electronic and structural properties of the colloidal aggregates by using the specificity of DNA interactions to direct the interactions between particles of different size and composition.
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            "Nanoantibiotics": a new paradigm for treating infectious diseases using nanomaterials in the antibiotics resistant era.

            Ae Jung Huh, Young Kwon (2011)
            Despite the fact that we live in an era of advanced and innovative technologies for elucidating underlying mechanisms of diseases and molecularly designing new drugs, infectious diseases continue to be one of the greatest health challenges worldwide. The main drawbacks for conventional antimicrobial agents are the development of multiple drug resistance and adverse side effects. Drug resistance enforces high dose administration of antibiotics, often generating intolerable toxicity, development of new antibiotics, and requests for significant economic, labor, and time investments. Recently, nontraditional antibiotic agents have been of tremendous interest in overcoming resistance that is developed by several pathogenic microorganisms against most of the commonly used antibiotics. Especially, several classes of antimicrobial nanoparticles (NPs) and nanosized carriers for antibiotics delivery have proven their effectiveness for treating infectious diseases, including antibiotics resistant ones, in vitro as well as in animal models. This review summarizes emerging efforts in combating against infectious diseases, particularly using antimicrobial NPs and antibiotics delivery systems as new tools to tackle the current challenges in treating infectious diseases. Copyright © 2011 Elsevier B.V. All rights reserved.
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              In vitro toxicity of nanoparticles in BRL 3A rat liver cells.

              S. Hussain, K. L. Hess, J Gearhart … (2005)
              This study was undertaken to address the current deficient knowledge of cellular response to nanosized particle exposure. The study evaluated the acute toxic effects of metal/metal oxide nanoparticles proposed for future use in industrial production methods using the in vitro rat liver derived cell line (BRL 3A). Different sizes of nanoparticles such as silver (Ag; 15, 100 nm), molybdenum (MoO(3); 30, 150 nm), aluminum (Al; 30, 103 nm), iron oxide (Fe(3)O(4); 30, 47 nm), and titanium dioxide (TiO(2); 40 nm) were evaluated for their potential toxicity. We also assessed the toxicity of relatively larger particles of cadmium oxide (CdO; 1 microm), manganese oxide (MnO(2); 1-2 microm), and tungsten (W; 27 microm), to compare the cellular toxic responses with respect to the different sizes of nanoparticles with different core chemical compositions. For toxicity evaluations, cellular morphology, mitochondrial function (MTT assay), membrane leakage of lactate dehydrogenase (LDH assay), reduced glutathione (GSH) levels, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were assessed under control and exposed conditions (24h of exposure). Results showed that mitochondrial function decreased significantly in cells exposed to Ag nanoparticles at 5-50 microg/ml. However, Fe(3)O(4), Al, MoO(3) and TiO(2) had no measurable effect at lower doses (10-50 microg/ml), while there was a significant effect at higher levels (100-250 microg/ml). LDH leakage significantly increased in cells exposed to Ag nanoparticles (10-50 microg/ml), while the other nanoparticles tested displayed LDH leakage only at higher doses (100-250 microg/ml). In summary the Ag was highly toxic whereas, MoO(3) moderately toxic and Fe(3)O(4), Al, MnO(2) and W displayed less or no toxicity at the doses tested. The microscopic studies demonstrated that nanoparticle-exposed cells at higher doses became abnormal in size, displaying cellular shrinkage, and an acquisition of an irregular shape. Due to toxicity of silver, further study conducted with reference to its oxidative stress. The results exhibited significant depletion of GSH level, reduced mitochondrial membrane potential and increase in ROS levels, which suggested that cytotoxicity of Ag (15, 100 nm) in liver cells is likely to be mediated through oxidative stress.
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                Author and article information

                Contributors
                Ecaterina Andronescu: Role: Academic Editor
                Alexandru Mihai Grumezescu: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Molecules
                Journal ID (iso-abbrev): Molecules
                Journal ID (publisher-id): molecules
                Title: Molecules
                Publisher: MDPI
                ISSN (Electronic): 1420-3049
                Publication date (Electronic): 01 July 2016
                Publication date Collection: July 2016
                Volume: 21
                Issue: 7
                Electronic Location Identifier: 867
                Affiliations
                [1 ]Department of Microbiology and Parasitology, University Santiago de Compostela, Galicia 15782, Spain; eva.torres.sangiao@ 123456gmail.com
                [2 ]Department of Microbiology and Immunology, Faculty of Biology, University of Bucharest, Bucharest 060101, Romania; alina_m_h@ 123456yahoo.com
                [3 ]Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, Bucharest 060042, Romania
                [4 ]Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens (UGA), GA 30602, USA
                Author notes
                [* ]Correspondence: mcarges@ 123456gmail.com or mcgestal@ 123456uga.edu ; Tel.: +1-706-202-5304
                Article
                Publisher ID: molecules-21-00867
                DOI: 10.3390/molecules21070867
                PMC ID: 6273484
                PubMed ID: 27376260
                SO-VID: 3573f94a-4c4d-4309-8d4d-3efd2b53d3c6
                Copyright © © 2016 by the authors.
                License:

                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
                Date received : 25 May 2016
                Date accepted : 25 June 2016
                Categories
                Subject: Review

                Keywords: nanoparticles,vaccines,microbiology diagnosis,biofilm,antibiotic resistance
                Data availability:
                Keywords: nanoparticles, vaccines, microbiology diagnosis, biofilm, antibiotic resistance

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