Wide-Field Multiplexed Imaging of EGFR-Targeted Cancers Using Topical Application of NIR SERS Nanoprobes

Abstract

This advancement represents a key step towards sensitive wide-field Raman endoscopic imaging of multiple biomarkers for early and accurate diagnosis of EGF receptor-expressing tumors of different internal organs.

Cancer characterization and diagnosis with SERS-encoded particles

“…In fact, it has been demonstrated that SEPs can adhere to tumor tissues in less than minutes, although the nonspecifically adsorbed SEPs must be removed by washing the tissue with serum (Wang et al 2014a). The obstacle set by the high background distribution of non-specifically bound nanoparticles can be overcome by implementing ratiometric approaches where one of the SEP type in the particle cocktail is used as a nonspecific internal reference to visually enhance the preferential adhesion of other targeting nanoparticles on tumor tissues (Mallia et al 2015;Oseledchyk et al 2017;Pallaoro et al 2011). Implementation of these methods is rather straightforward for SERS imaging due to the high degree of multiplexing provided by the narrow Raman linewidths.…”

“…While active targeting methods have proven to significantly reduce the dissipation of SEPs to healthy tissues and organs with respect to passive approaches, still toxicity and clearance issues remain major concerns associated with the systemic route of administration (such as via intravenous injections). Thus, when allowed, alternative strategies to circumvent these problems have been exploited, including topical spray-like applications (Mallia et al 2015;Zavaleta et al 2013) and direct intratumoral injections (Dinish et al 2014;Oseledchyk et al 2017).…”

“…These administration routes also allow for shortening the relatively long accumulation time of systemic deliveries as well as reducing the amount of administered SEPs and the impact of nonspecific background signal (Mallia et al 2015). Further, the intrinsic limitations imposed by the relatively large hydrodynamic size of SEPs (normally > 100 nm) on both the efficient circulation and extravasation from the bloodstream into cancer tissues, and the successful hepatic and renal clearance from the body, can be turned into a positive leverage in topical applications.…”

“…Further, the intrinsic limitations imposed by the relatively large hydrodynamic size of SEPs (normally > 100 nm) on both the efficient circulation and extravasation from the bloodstream into cancer tissues, and the successful hepatic and renal clearance from the body, can be turned into a positive leverage in topical applications. In this case, the transfer of SEPs into the bloodstream is minimal, retaining local high concentration at the administered area (Jokerst et al 2011;Mallia et al 2015), while, such as in the case of intrarectally applications, the majority of the nanoparticle clearing is achieved after 24 h without systemic circulation crossing .…”

“…Clearly, topical administrations of SEPs are not as much as valuable for deep tissue imaging as compared to their integration into surface imaging of tissues (Mallia et al 2015), such as those revisiting, within the frame of SERS, the well-established "sprayand-image" procedure in endoscopy using chromogenic dyes to highlight pathologic lesions (Mallia et al 2015).…”