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      Multifunctional Gold Nanoparticles for Improved Diagnostic and Therapeutic Applications: A Review

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          Abstract

          The medical properties of metals have been explored for centuries in traditional medicine for the treatment of infections and diseases and still practiced to date. Platinum-based drugs are the first class of metal-based drugs to be clinically used as anticancer agents following the approval of cisplatin by the United States Food and Drug Administration (FDA) over 40 years ago. Since then, more metals with health benefits have been approved for clinical trials. Interestingly, when these metals are reduced to metallic nanoparticles, they displayed unique and novel properties that were superior to their bulk counterparts. Gold nanoparticles (AuNPs) are among the FDA-approved metallic nanoparticles and have shown great promise in a variety of roles in medicine. They were used as drug delivery, photothermal (PT), contrast, therapeutic, radiosensitizing, and gene transfection agents. Their biomedical applications are reviewed herein, covering their potential use in disease diagnosis and therapy. Some of the AuNP-based systems that are approved for clinical trials are also discussed, as well as the potential health threats of AuNPs and some strategies that can be used to improve their biocompatibility. The reviewed studies offer proof of principle that AuNP-based systems could potentially be used alone or in combination with the conventional systems to improve their efficacy.

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          An mRNA Vaccine against SARS-CoV-2 — Preliminary Report

          Abstract Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein. Methods We conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 μg, 100 μg, or 250 μg. There were 15 participants in each dose group. Results After the first vaccination, antibody responses were higher with higher dose (day 29 enzyme-linked immunosorbent assay anti–S-2P antibody geometric mean titer [GMT], 40,227 in the 25-μg group, 109,209 in the 100-μg group, and 213,526 in the 250-μg group). After the second vaccination, the titers increased (day 57 GMT, 299,751, 782,719, and 1,192,154, respectively). After the second vaccination, serum-neutralizing activity was detected by two methods in all participants evaluated, with values generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens. Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-μg dose group reported one or more severe adverse events. Conclusions The mRNA-1273 vaccine induced anti–SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 ClinicalTrials.gov number, NCT04283461).
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            Calculated absorption and scattering properties of gold nanoparticles of different size, shape, and composition: applications in biological imaging and biomedicine.

            The selection of nanoparticles for achieving efficient contrast for biological and cell imaging applications, as well as for photothermal therapeutic applications, is based on the optical properties of the nanoparticles. We use Mie theory and discrete dipole approximation method to calculate absorption and scattering efficiencies and optical resonance wavelengths for three commonly used classes of nanoparticles: gold nanospheres, silica-gold nanoshells, and gold nanorods. The calculated spectra clearly reflect the well-known dependence of nanoparticle optical properties viz. the resonance wavelength, the extinction cross-section, and the ratio of scattering to absorption, on the nanoparticle dimensions. A systematic quantitative study of the various trends is presented. By increasing the size of gold nanospheres from 20 to 80 nm, the magnitude of extinction as well as the relative contribution of scattering to the extinction rapidly increases. Gold nanospheres in the size range commonly employed ( approximately 40 nm) show an absorption cross-section 5 orders higher than conventional absorbing dyes, while the magnitude of light scattering by 80-nm gold nanospheres is 5 orders higher than the light emission from strongly fluorescing dyes. The variation in the plasmon wavelength maximum of nanospheres, i.e., from approximately 520 to 550 nm, is however too limited to be useful for in vivo applications. Gold nanoshells are found to have optical cross-sections comparable to and even higher than the nanospheres. Additionally, their optical resonances lie favorably in the near-infrared region. The resonance wavelength can be rapidly increased by either increasing the total nanoshell size or increasing the ratio of the core-to-shell radius. The total extinction of nanoshells shows a linear dependence on their total size, however, it is independent of the core/shell radius ratio. The relative scattering contribution to the extinction can be rapidly increased by increasing the nanoshell size or decreasing the ratio of the core/shell radius. Gold nanorods show optical cross-sections comparable to nanospheres and nanoshells, however, at much smaller effective size. Their optical resonance can be linearly tuned across the near-infrared region by changing either the effective size or the aspect ratio of the nanorods. The total extinction as well as the relative scattering contribution increases rapidly with the effective size, however, they are independent of the aspect ratio. To compare the effectiveness of nanoparticles of different sizes for real biomedical applications, size-normalized optical cross-sections or per micron coefficients are calculated. Gold nanorods show per micron absorption and scattering coefficients that are an order of magnitude higher than those for nanoshells and nanospheres. While nanorods with a higher aspect ratio along with a smaller effective radius are the best photoabsorbing nanoparticles, the highest scattering contrast for imaging applications is obtained from nanorods of high aspect ratio with a larger effective radius.
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              Doxil®--the first FDA-approved nano-drug: lessons learned.

              Doxil®, the first FDA-approved nano-drug (1995), is based on three unrelated principles: (i) prolonged drug circulation time and avoidance of the RES due to the use of PEGylated nano-liposomes; (ii) high and stable remote loading of doxorubicin driven by a transmembrane ammonium sulfate gradient, which also allows for drug release at the tumor; and (iii) having the liposome lipid bilayer in a "liquid ordered" phase composed of the high-T(m) (53 °C) phosphatidylcholine, and cholesterol. Due to the EPR effect, Doxil is "passively targeted" to tumors and its doxorubicin is released and becomes available to tumor cells by as yet unknown means. This review summarizes historical and scientific perspectives of Doxil development and lessons learned from its development and 20 years of its use. It demonstrates the obligatory need for applying an understanding of the cross talk between physicochemical, nano-technological, and biological principles. However, in spite of the large reward, ~2 years after Doxil-related patents expired, there is still no FDA-approved generic "Doxil" available. Copyright © 2012 Elsevier B.V. All rights reserved.
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                Author and article information

                Contributors
                amadiehe@uwc.ac.za
                memeyer@uwc.ac.za
                Journal
                Nanoscale Res Lett
                Nanoscale Res Lett
                Nanoscale Research Letters
                Springer US (New York )
                1931-7573
                1556-276X
                5 December 2021
                5 December 2021
                2021
                : 16
                : 174
                Affiliations
                [1 ]GRID grid.8974.2, ISNI 0000 0001 2156 8226, Department of Science and Innovation (DSI)/Mintek Nanotechnology Innovation Centre (NIC) Biolabels Node, Department of Biotechnology, , University of the Western Cape, ; Private Bag X17, Bellville, 7535 South Africa
                [2 ]GRID grid.8974.2, ISNI 0000 0001 2156 8226, Nanobiotechnology Research Group, Department of Biotechnology, , University of the Western Cape, ; Bellville, South Africa
                [3 ]GRID grid.411921.e, ISNI 0000 0001 0177 134X, Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, , Cape Peninsula University of Technology, ; Bellville, South Africa
                [4 ]GRID grid.8974.2, ISNI 0000 0001 2156 8226, Organometallics and Nanomaterials, Department of Chemical Sciences, , University of the Western Cape, ; Bellville, South Africa
                Author information
                http://orcid.org/0000-0001-7175-5388
                Article
                3632
                10.1186/s11671-021-03632-w
                8645298
                34866165
                112ef267-6e5e-4db0-87cb-bd449506d71d
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 30 June 2021
                : 21 November 2021
                Categories
                Nano Review
                Custom metadata
                © The Author(s) 2021

                Nanomaterials
                bio-functionalization,drug delivery,drug targeting,gold nanoparticles,metal-based therapy,multimodal systems

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