Intracellular Behavior of Nanoparticles Based on their Physicochemical Properties

Intracellular Behavior of Nanoparticles Based on their Physicochemical Properties

Charmainne Cruje (Ryerson University, Canada), Darren Yohan (Ryerson University, Canada), Celina Yang (Ryerson University, Canada) and Devika B. Chithrani (Ryerson University, Canada)
DOI: 10.4018/978-1-5225-3158-6.ch047
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This chapter addresses physicochemical properties that affect Nanoparticle (NP) intracellular behavior using Gold NPs (GNPs) as a model system. The main objective is to outline what is known about the effect of GNP size, shape, and surface properties on cellular uptake and intracellular pathway. The authors propose that the entry of GNPs into cells is related to its effectiveness in applications that favor intracellular localization of such GNPs. The authors also discuss how such properties are used to optimize GNP designs for medical applications. Finally, the authors discuss how GNPs may improve disease diagnosis and treatment. Furthermore, how they may be incorporated or used as alternatives to current treatment options is defined.
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GNPs have been receiving significant attention for use in cancer diagnosis and treatment (Brown et al., 2010; Chithrani et al., 2010; El-Sayed, Huang, & El-Sayed, 2006; Huang, El-Sayed, Qian, El-Sayed, 2006; Loo, Lowery, Halas, West, & Drezek, 2005; Wijaya, Schaffer, Pallares, & Hamad-Schifferli, 2009; Zhang et al., 2009; Zheng & Sanche, 2009). There have been a number of studies investigating the potential cytotoxic effects, and intracellular behavior of GNPs as a function of their physicochemical properties (Chithrani & Chan, 2007; Chithrani, Ghazani, & Chan, 2006; Connor, Mwamuka, Gole, Murphy, & Wyatt, 2005; Jiang, Kim, Rutka, & Chan, 2008; Shukla et al., 2005). Most of these investigations have used static methods such as inductively coupled surface plasmon atomic emission spectroscopy, transmission electron microscopy (TEM), and fixed-cell confocal microscopy. However, understanding of the cytoplasmic transport of gold nanostructures in four dimensions (space and time) provides new insight into their intracellular behavior. As initial steps in this direction, surface-enhanced Raman spectroscopy (SERS) and confocal microscopy have been used to probe the interactions of NPs with the cellular environment (Chithrani, Stewart, Allen, & Jaffray, 2009; Huff, Hansen, Zhao, Chen, & Wei, 2007; Kneipp, Kneipp, McLaughlin, Brown, & Kneipp, 2006; Kumar, Harrison, Richards-Kortum, & Sokolov, 2007). Physicochemical properties of NPs including size, shape, surface charge and surface chemistry have been identified as strongly affecting the cellular uptake efficiency. The size and shape of GNPs can be tailored to range between 2-100 nm and their surface properties allow for facile functionalization and targeting to specific biological structures such as the nucleus (Berry, de la Fuente, Mullin, Chu, & Curtis, 2007; Feldherr, Kallenbach, & Schultz, 1984; Jiang et al., 2008; Nativo, Prior, & Brust, 2008; Oyelere, Chen, Huang, El-Sayed, & El-Sayed, 2007; Souza et al., 2006; Tkachenko et al., 2004). In addition, the ability to produce various delivery forms like liposomes, micelles or dendrimers has increased the application scope of GNPs (Carrot et al., 1998; Garcia, Baker, & Crooks, 1999; Mohamed, Ismail, Link, & El-Sayed, 1998; Sung-Hee, Seong-Geun, Ji-Young, & Sung-Sik, 2006). These advantages, along with their biocompatibility, have motivated interest in employing gold nanoparticles in cell imaging, targeted drug and gene delivery, and biosensing (Bergen et al., 2006; Han et al., 2006; Kneipp et al., 2006; Kumar et al., 2007; Sandhu, McIntosh, Simard, Smith, & Rotello, 2002; Shukla et al., 2005; Sokolov et al., 2003).

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