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Gold Nanoparticles Enlighten the Future of Cancer Theranostics Open Access to Scientific and Medical Research DOI Journal name: International Journal of Nanomedicine Article Designation: Review Year: 2017 Volume: 12 International Journal of Nanomedicine Dovepress Running head verso: Guo et al Running head recto: Gold nanoparticles enlighten the future of cancer theranostics open access to scientific and medical research DOI: http://dx.doi.org/10.2147/IJN.S140772 Open Access Full Text Article REVIEW Gold nanoparticles enlighten the future of cancer theranostics Jianfeng Guo1 Abstract: Development of multifunctional nanomaterials, one of the most interesting and Kamil Rahme2–4 advanced research areas in the field of nanotechnology, is anticipated to revolutionize cancer Yan He1 diagnosis and treatment. Gold nanoparticles (AuNPs) are now being widely utilized in bio- Lin-Lin Li5 imaging and phototherapy due to their tunable and highly sensitive optical and electronic Justin D Holmes3,4 properties (the surface plasmon resonance). As a new concept, termed “theranostics,” mul- Caitriona M O’Driscoll6 tifunctional AuNPs may contain diagnostic and therapeutic functions that can be integrated into one system, thereby simultaneously facilitating diagnosis and therapy and monitoring 1 School of Pharmaceutical Sciences, therapeutic responses. In this review, the important properties of AuNPs relevant to diagnostic Jilin University, Changchun, China; 2Department of Sciences, Faculty of and phototherapeutic applications such as structure, shape, optics, and surface chemistry are Natural and Applied Science, Notre described. Barriers for translational development of theranostic AuNPs and recent advances Dame University (Louaize), Zouk in the application of AuNPs for cancer diagnosis, photothermal, and photodynamic therapy Mosbeh, Lebanon; 3Department For personal use only. of Chemistry, Tyndall National are discussed. Institute, University College Cork, Keywords: multifunctional gold nanoparticles, cancer bioimaging, cancer photothermal and Cork, 4AMBER@CRANN, Trinity College Dublin, Dublin, Ireland; 5The photodynamic therapy First Hospital of Jilin University, Changchun, China; 6Pharmacodelivery Group, School of Pharmacy, University Introduction College Cork, Cork, Ireland Cancer, one of the leading causes of mortality worldwide, has caused approximately 8.8 million deaths in 2015 (www.who.int). The number of people who are diagnosed with this malignancy is expected to rise to 22 million annually in the next 2 decades (www.who.int). Despite the increased knowledge about the causes of cancer and the improved interventions to prevent and manage the disease, survival rates are still low mainly due to the delay in diagnosis, lack of effective therapeutics, and high incidence of relapse. International Journal of Nanomedicine downloaded from https://www.dovepress.com/ by 128.41.35.98 on 06-Jan-2018 As an emerging concept that facilitates simultaneous diagnosis and treatment, the implementation of theranostic nanomaterials (ie, metal and silica nanoparticles [NPs], Correspondence: Jianfeng Guo School of Pharmaceutical Sciences, Jilin liposomes, dendrimers, quantum dots, and carbon nanotubes) has great potential University, 1266, Fujin Road, Changchun for improved cancer treatment and reduced side effects.1–6 Among these, gold NPs 130021, China Tel +86 431 8561 9716 (AuNPs) exhibit favorable physical properties and tailored surface functionaliza- Fax +86 431 8561 9252 tion, providing a potential platform for developing cancer theranostics. This review Email [email protected] provides a comprehensive overview of AuNPs as emerging nanomaterials for future Caitriona M O’Driscoll cancer theranostics. In this regard, the key physicochemical properties of AuNPs Pharmacodelivery Group, School of such as structure, shape, optics, and surface chemistry are discussed. In addition, Pharmacy, University College Cork, College Road, Cork, Ireland various AuNP-based diagnostic and phototherapeutic strategies under investigation Tel +353 21 490 1396 are critically evaluated, with a particular emphasis on those developed to overcome Fax +353 21 490 1656 Email [email protected] delivery barriers. submit your manuscript | www.dovepress.com International Journal of Nanomedicine 2017:12 6131–6152 6131 Dovepress © 2017 Guo et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you http://dx.doi.org/10.2147/IJN.S140772 hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Powered by TCPDF (www.tcpdf.org) 1 / 1 Guo et al Dovepress Key properties of AuNPs for tetrachloroauric acid (gold [III] chloride [HAuCl4]) in diagnosis and phototherapy water, and later Frens9 improved the formation using a Types of AuNPs slightly modified method. Recently, AuNPs have been pro- Colloidal AuNPs were first produced in 1857 by Faraday,7 duced with various sizes and shapes (ie, gold nanospheres, where the “fine particles” were formed from the reduc- nanorods, nanocages, nanoshells, and nanostars), which tion of gold chloride by phosphorus and the stabilization are dependent upon the synthetic methods adopted for their of AuNPs by carbon disulfide. In 1951, Turkevich et al8 preparation (Figure 1; a summary of synthetic approaches reported the formation of colloidal AuNPs using triso- to obtain various gold nanostructures has been described 10–14 dium citrate (HOC(COONa)(CH2COONa)2) to reduce previously). $ $X13V 7KHUDQRVWLFDSSOLFDWLRQV • &HOOLPDJLQJ YLVLEOHOLJKWV $X • 377 YLVLEOHOLJKWV 1DQRVSKHUH • 'HOLYHU\RIWKHUDSHXWLFFDUJRV LHSKRWRVHQVLWL]HUV ±QP • 7XPRXULPDJLQJ HQKDQFHGUDGLDWLYHSURSHUW\1,5 $X$X • 377 HQKDQFHGQRQUDGLDWLYHSURSHUW\1,5 1DQRURG ±QP • 'HOLYHU\RIWKHUDSHXWLFFDUJRV LHSKRWRVHQVLWL]HUV $X • 7XPRXULPDJLQJ HQKDQFHGUDGLDWLYHSURSHUW\1,5 6LOLFD For personal use only. • 377 HQKDQFHGQRQUDGLDWLYHSURSHUW\1,5 • 3'7 XQLTXHVKDSHDQGVWUXFWXUH 1DQRVKHOO QP • 'HOLYHU\RIWKHUDSHXWLFFDUJRV LHSKRWRVHQVLWL]HUV • 7XPRXULPDJLQJ HQKDQFHGUDGLDWLYHSURSHUW\1,5 • 377 HQKDQFHGQRQUDGLDWLYHSURSHUW\1,5 • 3'7 XQLTXHVKDSHDQGVWUXFWXUH 1DQRFDJH ±QP • 'HOLYHU\RIWKHUDSHXWLFFDUJRV LHSKRWRVHQVLWL]HUV % • ,PSURYHGVWDELOLW\ 'UXJ International Journal of Nanomedicine downloaded from https://www.dovepress.com/ by 128.41.35.98 on 06-Jan-2018 7DUJHWLQJ OLJDQG 3URWHLQDQGSHSWLGH 6 • (QKDQFHG(35HIIHFW 6 6 6 6 $X 1XFOHLFDFLGV 3(* • &HOOVSHFLILFWDUJHWLQJ 6 6 6 ³6PDUW´OLQNHU • (QKDQFHG1,5DFWLYDWLRQ ,PDJLQJDJHQW 0XOWLIXQFWLRQDO VWUDWHJ\ • &RQWUROOHGGUXJUHOHDVH Figure 1 Development of theranostic AuNPs in the treatment of cancer. Notes: (A) Commonly used AuNPs can be categorized depending on the particle shape, including Au nanospheres, nanorods, nanoshells, and nanocages. These AuNPs with tunable optical and electronic properties and easy surface functionalizations have presented great potential for cancer bioimaging, PTT/PDT, and targeted drug delivery. (B) Functional components including stealth coating materials, bioresponsive moieties, bioactive targeting ligands, bioimaging agents, and therapeutic cargos can be integrated into one system, to achieve multifunctional AuNPs for future cancer treatment. Abbreviations: AuNPs, gold nanoparticles; EPR, enhanced penetration and retention; NIR, near-infrared; PDT, photodynamic therapy; PEG, polyethylene glycol; PTT, photothermal therapy. 6132 submit your manuscript | www.dovepress.com International Journal of Nanomedicine 2017:12 Dovepress Powered by TCPDF (www.tcpdf.org) 1 / 1 Dovepress Gold nanoparticles enlighten the future of cancer theranostics Gold nanospheres to generate Ag atoms followed by nanocrystals or seeds. Gold nanospheres (particle size 2–100 nm) are generally Silver nanostructures are utilized as the sacrificial template prepared after reducing HAuCl4 with the assistance of differ- and can be transformed into AuNPs with hollow structures ent reducing agents under various temperature and pressure. via the galvanic replacement.26 The molar ratio of Ag to Trisodium citrate (sometimes referred to simply as sodium HAuCl4 can be regulated to manipulate the diameter and citrate), for example, is a commonly used reducing and sta- wall thickness of resultant gold nanocages.26 bilizing agent, which is capable of generating monodisperse gold nanospheres with different particle sizes by adjusting Gold nanoshells the concentration of citrate.11 Gold nanoshells are normally composed of dielectric core The seeding growth strategy has been used to improve materials (ie, silica and polystyrene) coated by a thin gold monodispersity and avoid the formation of large AuNPs layer. Core materials such as silica and polystyrene have been with irregular shapes (diameter .50 nm), whereby large widely used to provide high stability and monodispersity.27 spherical AuNPs are produced by reducing HAuCl4 or Au These core materials can be tailored by varying the dimen- (III)-surfactant complexes onto the surface of preexist- sions of the core and/or the shell; normally, the core has a ing seeds using reducing agents such as hydroxylamine diameter ~100 nm and a thin shell of gold about several hydrochloride,15,16 ascorbic acid,17 2-mercaptosuccinic acid,18 nanometers (~1–20 nm).28,29 hydroquinone,19
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