Development of Chitosan Oligosaccharide-Modified Gold Nanorods for in Vivo Targeted Delivery and Noninvasive Imaging by NIR Irradiation

Abstract

In the present study, we demonstrate the synthesis and applications of multifunctional gold nanorod-based probes for specific targeting and noninvasive imaging based on localized heating generated by gold nanorods after NIR irradiation. The structural design of the probe consists of MUA (11-mercaptoundecanoic acid)-capped gold nanorods covalently linked with low-molecular-weight chitosan oligosaccharide (M(w) ~5000) via carbodiimide (EDC) coupling agent. This surface modification is performed for complete replacement of toxic CTAB (hexadecyltrimethyl-ammonium chloride) and acid-responsive delivery of gold nanorods in acidic environment as known to be present at tumor surrounding areas. The resulting chitosan oligosaccharide-modified gold nanorods (CO-GNRs) were further conjugated with tumor targeting monoclonal antibody against EGFR (epidermal growth factor receptor) to provide localized targeting functionality owing to the overexpression of EGFR in human oral adenosquamous carcinoma cell line CAL 27. Initial in vitro and in vivo toxicity assessments indicated that CO-GNRs did not induce any significant toxicity and are thus suitable for biological applications. Furthermore, selective targeting and accumulation of CO-GNRs were observed in vitro via two-photon luminescence imaging studies in CAL 27, which was also observed through in vivo targeting studies performed via NIR (near-infrared) laser irradiation in CAL 27 xenografts of BALB/c nude mice. Hence, the CO-GNRs that we have developed are biocompatible and nontoxic and can be a potential candidate for in vivo targeted delivery, noninvasive imaging based on localized hyperthermia, and photothermal-related therapies.

Gold Nanorods Based Platforms for Light-Mediated Theranostics

“…The anti-EGFR-AuNRs were observed at depths up to 100 μm in the tumors. Selective targeting and accumulation of chitosan oligosaccharide-modified AuNRs were also observed in vitro via TPL imaging studies in human oral adenosquamous carcinoma cell line (CAL 27) 11, consistent with in vivo targeting studies performed via NIR laser irradiation in CAL 27 xenograft tumors (Figure 3A).…”

Near Infrared Fluorescence Imaging in Nano-Therapeutics and Photo-Thermal Evaluation

“…Photothermal imaging of CAL 27 xenografted tumors displayed significant temperature increments (~up to 71 °C) specifically at the tumor microenvironment after NIR irradiation, which is well suited for PTT. Modified nanoparticles also did not display any associated toxic effect in vivo [64]. Cheng et al reported a study of ultrasmall (10 nm) dendrimer-stabilized gold nanorods (DSAuNRs) for photothermal destruction of cancer cells.…”

Significantly Enhanced Third Harmonic Generation Using Individual Au Nanorods Coated With Gain Materials

“…Both Au and Ag NPs with various shapes can serve as the LSPR core for the core-shell structure. However, only Au NR will be considered as an example in the present paper owing to its tunable absorption peak, which can be moved into the NIR region by increasing the corresponding aspect ratio [33]. Moreover, the Au NR is surrounded by the gain medium that overlaps spatially with the hot-spot of the local plasmonic field and whose gain spectrum overlaps spectrally with the resonant absorption.…”