Implantable Photothermal Agents based on Gold Nanorods-Encapsulated Microcube.

Gold nanorods (GNRs) are of great interest in cancer therapy given their ability to ablate tumor cells using deep tissue-penetrating near-infrared light. GNRs coated with tumor-specific moieties have the potential to target tumor tissue to minimize damage to normal tissue. However, perfect targeting is difficult to achieve given that nanoparticles could be broadly dispersed inside the body. Moreover, interaction between targeting groups and biological molecules could lower targeting abilities, resulting in off-target accumulation which might produce nanotoxicity. Here we introduce GNR-encapsulated microcubes (GNR@MCs) that can be utilized as implantable photothermal agents. GNR@MCs are created by encapsulating GNRs in polymeric networks via stop flow lithography (SFL), a one-phase synthesis technique which allows for creation of surfactant-free, uniform particles, and injection of GNR@MCs into the body after a simple rinse step. GNRs are highly packed and firmly encapsulated inside MCs, and entrapped GNRs exhibit optical properties comparable to that of unbound GNRs and photothermal efficiency (58%) in line with that of nano-sized agents (51-95%). Photothermal ablation in murine models is achieved using GNR@MCs stably implanted into the tumor tissue, which suggests that GNR@MCs can be a safe and effective platform for cancer therapy.

Photothermal ablation of cancer cells using self-doped polyaniline nanoparticles.

Water-stable confined self-doping polyaniline nanocomplexes are successfully fabricated by nano-assembly using lauric acid both as a stabilizer and as a localized dopant. In particular, the colloidal stability of the polyaniline nanocomplexes in neutral pH and the photothermal potential by near-infrared light irradiation are characterized. We demonstrate that confined self-doping polyaniline nanocomplexes as a photothermal nanoagent are preserved in the doped state even at a neutral pH. Finally, confined self-doping polyaniline nanocomplexes aided by lauric acid are successfully applied for the photothermal ablation of cancer cells.

Fluorescent iodized emulsion for pre- and intraoperative sentinel lymph node imaging: validation in a preclinical model.

PURPOSE: To validate the usefulness of a newly developed tracer for preoperative gastric sentinel lymph node (LN) (SLN) mapping and intraoperative navigation after a single preoperative submucosal injection in rat and beagle models. MATERIALS AND METHODS: This study was approved by the Experimental Animal Ethical Committee of Yonsei University College of Medicine according to the eighth edition of the Guide for the Care and Use of Laboratory Animals published in 2011. An emulsion was developed that contained indocyanine green in iodized oil, which can be visualized with both computed tomography (CT) and near-infrared (NIR) optical imaging and has the property of delayed washout. This emulsion was injected into the footpad of rats (n = 6) and the gastric submucosa of beagles (n = 8). CT lymphography was performed. The degree of enhancement of popliteal LNs was measured in rats, and the enhancing LNs were identified and the degree of enhancement of the enhancing LNs was measured in beagles. Next, NIR imaging was performed in beagles during open, laparoscopic, and robotic surgery to identify LNs containing the fluorescent signals of indocyanine green. The enhanced LNs detected with CT lymphography and NIR imaging were matched to see if they corresponded. RESULTS: Preoperative CT lymphography facilitated SLN mapping, and 26 SLNs were identified in eight beagles. NIR imaging enabled high-spatial-resolution visualization of both SLNs and the intervening lymphatic vessels and was useful for intraoperative SLN navigation. CONCLUSION: SLN mapping with fluorescent iodized oil emulsion is effective and feasible for both CT and NIR imaging.

Aptamer-conjugated gold nanorod for photothermal ablation of epidermal growth factor receptor-overexpressed epithelial cancer.

Biomarker-specific photothermal nanoparticles that can efficiently sense markers that are overexpressed in distinguished adenocarcinomas have attracted much interest in an aspect of efficacy increase of cancer treatment. We demonstrated a promising prospect of a smart photothermal therapy agent employing anti-epidermal growth factor receptor aptamer (AptEGFR)-conjugated polyethylene glycol (PEG) layted gold nanorods (AptEGFR-PGNRs). The cetyltrimethylammonium bromide bilayer on GNRs was replaced with heterobifunctional PEG (COOH-PEG-SH) not only to serve as a biocompatible stabilizer and but also to conjugate AptEGFR. Subsequently, to direct photothermal therapy agent toward epithelial cancer cells, the carboxylated PEGylated GNRs (PGNRs) were further functionalized with AptEGFR using carbodiimide chemistry. Then, to assess the potential as biomarker-specific photothermal therapy agent of synthesized AptEGFR-PGNRs, the optical properties, biocompatibility, colloidal stability, binding affinity, and epicellial cancer cell killing efficacy in vitro/in vivo under near-infrared laser irradiation were investigated. As a result, AptEGFR-PGNRs exhibit excellent tumor targeting ability and feasibility of effective photothermal ablation cancer therapy.

Targetable gold nanorods for epithelial cancer therapy guided by near-IR absorption imaging.

Well-designed nanoparticle-mediated, image-guided cancer therapy has attracted interest for increasing the efficacy of cancer treatment. A new class of smart theragnostic nanoprobes employing cetuximab (CET)-conjugated polyethylene glycol (PEG)ylated gold nanorods (CET-PGNRs) is presented; these nanoprobes target epithelial cancer cells using near-infrared light. The cetyltrimethylammonium bromide bilayer on GNRs is replaced with heterobifunctional PEG (COOH-PEG-SH) to serve as a biocompatible stabilizer and to increase specificity. The carboxylated GNRs are further functionalized with CET using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC-NHS) chemistry. To assess the potential of such GNRs, their optical properties, biocompatibility, colloidal stability, in vitro/in vivo binding affinities for cancer cells, absorption imaging, and photothermal therapy effects are investigated. CET-PGNRs exhibit excellent tumor targeting ability and strong potential for simultaneous absorption imaging and photothermal ablation of epithelial cancer cells.

Gold nanostructures as photothermal therapy agent for cancer.

Well-designed photothermal nanostructures have attracted many scientists pursuing a better means to accurately diagnose cancer and assess the efficacy of treatment. Recently, gold-based nanostructures (nanoshells, nanorods and nanocages) have enabled photothermal ablation of cancer cells with near-infrared (NIR) light without damaging normal human tissues and in particular, animal studies and early clinical testing showed the great promise for these materials. In this review article, we first discuss the mechanism of the cellular death signaling by thermal stress and introduce the intrinsic properties of gold nanostructures as photothermal agent for cancer treatment. Then the overview follows for evolving researches for the synthesis of various types of gold nanostructures and for their biomedical applications. Finally we introduce the optimized therapeutic strategies involving nanoparticle surface modification and laser operation method for an enhanced accumulation of gold nanostructures to the target cancer as well as for an effective cancer cell ablation.

Multifunctional nanoparticles for combined doxorubicin and photothermal treatments.

To facilitate combined doxorubicin and photothermal treatments, we developed doxorubicin-loaded poly(lactic-co-glycolic acid)-gold half-shell nanoparticles (DOX-loaded PLGA-Au H-S NPs) by depositing Au films on DOX-loaded PLGA NPs. As the PLGA NPs biodegraded, DOX was released, and heat was locally generated upon near-infrared (NIR) irradiation due to NIR resonance of DOX-loaded PLGA H-S NPs. Compared with chemotherapy or photothermal treatment alone, the combined treatment demonstrated a synergistic effect, resulting in higher therapeutic efficacy and shorter treatment times. Since our NPs selectively deliver both heat and drug to tumorigenic regions, they may improve the therapeutic effectiveness with minimal side effects.