REVIEW ARTICLE Trends of Gold Nanoparticle-based Drug Delivery System in Cancer Therapy Giimel Ajnai 1 , Amy Chiu 1 , Tzuchun Kan 1 , Chun-Chia Cheng 2 , Teh-Hua Tsai 3 , Jungshan Chang 1 * 1 Graduate Institute of Medical Sciences, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 2 Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, Taiwan 3 Department of Chemical Engineering and Biotechnology, National Taipei University of Technology Taipei, Taiwan article info Article history: Received: Oct 2, 2014 Revised: Oct 16, 2014 Accepted: Oct 20, 2014 KEY WORDS: gold nanoparticles; nanomedicine; reticuloendothelial system Following surgical removal of malignant tumors, chemotherapeutic intervention usually is subsequently applied in patients with advanced stages of cancer. Most chemotherapeutic drugs are intravenously injected into patients, leading to systemic cytotoxicity in organs and tissues, including healthy tissue and tumors. Currently, it has been demonstrated that gold nanoparticles can easily penetrate blood vessels and tissue barriers into tumor foci, which indicates gold nanoparticles as a more effective drug carrier with great merits in reducing cytotoxicity and economic burden in patients. Moreover, gold nanoparticles display several unique characterizations with multiple functions in therapeutics, imaging, and surface modification, suggesting gold nanoparticles may become effective antitumor drug carriers. In this review article, we discuss the limitations and applications of gold nanoparticles in surface modification, tar- geting strategy, and safety considerations. Copyright © 2014, Taipei Medical University. Published by Elsevier Taiwan LLC. All rights reserved. 1. Introduction Cancer is the leading cause of death worldwide. According to the United States cancer statistic reports, one of every four deaths in the United States is caused by cancer. 1 Chemotherapeutics are commonly used in current practice to treat cancer via intravenous administration but also to elicit toxicity to normal cells, leading to severe side effects in patients. Therefore, a new and improved therapeutic method to target tumor foci coupled with enhanced cytotoxicity on cancer cells and decreased side effects is needed. Recently, inorganic nanoparticles such as gold nanoparticles (GNPs) have been explored and exploited as a promising candidate for various biotechnology applications because of their unique characterizations. GNPs have been used as nanobiomaterials for molecular imag- ing and drug delivery in recent years. 2 Gold nanoparticle conju- gates express unique properties such as increased binding affinity and selective targeting to specific tissue or cells when delivered systemically. 3 Because gold nanoparticles can be modified in different ways by binding specific receptors coupled with various forms of therapeutics, there is a wide range of research and nanoparticle-based therapeutic methods under development for cancer. 4,5 The delivery of GNP-conjugated drugs have a higher perfusion rate in targeting tumor foci, leading to reducing anti- tumor drug dosage for treatments and lower toxicity to normal tissues coupled with less side effects. In this review, we discuss various drug delivery systems of GNPs in cancer, including targeting approaches, modified conjugates and safety issue using nanoparticles in GNP-based drug delivering system. 2. Nanotechnology and nanomedicine Nanotechnology is continuously being extended in the field of medicine to reach maximum therapeutic possibility and reduce side effects of clinically used agents. The history of nanotechnology began in the 1950s, when the first polymer drug conjugate was successfully schemed by Jatzkewitz, 6 followed by the liposome discoveries of Bangham and Horne, 7 and Bangham et al 8 during the mid 1960s. Current nanotechnology applications in medicine led to the emergence of a new domain in science known as nano- medicine, offering some exciting prospects such as improvement in diagnosis, monitoring, prevention, and treatments of disease using selectively active drug carriers, diagnostic agents, and pharma- ceutical moieties to a target site. 9 Various types of nanoparticles Conflicts of interest: None. * Corresponding author. Jungshan Chang, Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wusing Street, Sinyi District, Taipei 11031, Taiwan. E-mail: J. Chang <js.chang@tmu.edu.tw> Contents lists available at ScienceDirect Journal of Experimental and Clinical Medicine journal homepage: http://www.jecm-online.com http://dx.doi.org/10.1016/j.jecm.2014.10.015 1878-3317/Copyright © 2014, Taipei Medical University. Published by Elsevier Taiwan LLC. All rights reserved. J Exp Clin Med 2014;6(6):172e178