We evaluated cellular responses to polymer-treated gold nanorods, which were synthesized using the standard wet-chemistry method that utilizes hexadecyltrimethylammonium bromide (CTAB). The nanorod dispersions were coated with either polystyrene sulfonate (PSS) or polyethylene glycol (PEG). Two sizes of nanorods were tested, with optical responses peaking at 628 and 773 nm. The cells were from mammary adenocarcinoma (SKBR3), Chinese Hamster Ovary (CHO), mouse myoblast (C2C12) and Human Leukemia (HL60) cell lines. Their mitochondrial function following exposure to the nanorods were assessed using the MTS assay. We found PEGylated particles to have superior biocompatibility compared with PSS-coated nanorods, which showed substantial cytotoxicity. Electron microscopy showed no cellular uptake of PEGylated particles compared with their PSS counterparts. PEGylated gold nanorods also exhibited better dispersion stability in the presence of cell growth medium; PSS-coated rods tended to flocculate or cluster. In the case of the PSS particles, toxicity correlated with surface area across the two sizes of nanorods studied.

Gold nanorods (AuNR) can be tailored to possess an intense and narrow longitudinal plasmon (LP) absorption peak in the far-red to near-infrared wavelength region, where tissue is relatively transparent to light. This makes AuNRs excellent candidates as contrast agents for photoacoustic imaging, and as photothermal therapeutic agents. The favorable optical properties of AuNR which depend on the physical parameters of shape, size and plasmonic coupling effects, are required to be stable during use. We investigate the changes that are likely to occur in these physical parameters in the setting of photothermal therapeutics, and the influence that these changes have on the optical properties and the capacity to achieve target cell death. To this end we study 3 sets of interactions: pulsed light with AuNR, AuNR with cells, and pulsed light with cells incubated with AuNR. In the first situation we ascertain the threshold value of fluence required for photothermal melting or reshaping of AuNR to shorter AuNR or nanospheres, which results in drastic changes in optical properties. In the second situation when cells are exposed to antibody-conjugated AuNR, we observe using transmission electron microscopy (TEM) that the particles are closely packed and clustered inside vesicles in the cells. Using dark-field microscopy we show that plasmonic interactions between AuNRs in this situation causes blue-shifting of the LP absorption peak. As a consequence, no direct lethal damage to cells can be inflicted by laser irradiation at the LP peak. On the other hand, using irradiation at the transverse peak (TP) wavelength in the green, at comparative fluences, extensive cell death can be achieved. We attribute this behavior on the one hand to the photoreshaping of AuNR into spheres and on the other hand to clustering of AuNR inside cells. Both effects create sufficiently high optical absorption at 532 nm, which otherwise would have been present at the LP peak. We discuss implications of these finding on the application of these particles in biomedicine.

Specific removal of the sentinel lymph node (SLN) during breast cancer surgery presents physicians with the opportunity to detect early metastatic disease. To increase the accuracy of intraoperative SLN detection, new methods with higher sensitivity and specificity are required. We have quantitatively compared conventional preoperative lymphoscintigraphy with albumin radiocolloids ((99m)Tc-NanoColl) with optical intraoperative guidance using the near infrared dye indocyanine green (ICG) in an orthotopic mouse model for metastatic breast cancer. Furthermore, we have applied a self-assembled multimodal complex, in which ICG is non-covalently bound to the albumin radiocolloid, to attain identical dynamics of the radioactive and optical components. The SLN specificity of the multimodal complex is similar to conventional lymphoscintigraphy, while the fluorescent signal-to-noise ratio is improved by 86% compared to ICG alone. In addition, the multimodal complex permits scintigraphic validation of the fluorescent findings. The multimodal ICG-(99m)Tc-NanoColl complex can be used both for lymphoscintigraphy by preoperative single photon emission computed tomography/computed tomography and for surgical navigation by intraoperative fluorescence imaging.

Abstract. To improve surgical guidance toward prostate draining lymph nodes, we investigate the potential of intraoperative fluorescence imaging and combined pre-and intraoperative multimodality imaging approaches. Transgenic adenocarcinoma mouse prostate mice with spontaneous prostate tumors are injected intratumorally with: 1. a cocktail of patent blue (Pb) and indocyanine green (ICG); 2. a cocktail of albumin radiocolloids ( 99m TcNanoColl), Pb, and ICG; or 3. a cocktail of radiolabeled albumin ( 99m Tc-Vasculosis), Pb, and ICG. The distribution of these imaging agents over the lymph nodes (LNs) are studied at different time points after injection. We find that at 60-min postinjection, ICG significantly improves the detection of the LNs compared to Pb, 53 versus 7%, respectively. Moreover, a cocktail of ICG and 99m Tc-NanoColl improves the fluorescent detection rate to 86%, equalling that of the clinically applied 99m Tc-NanoColl. A similar overlap is observed in our initial clinical pilot data. Fluorescent detection of the LNs using a ICG with 99m Tc-Vasculosis gives similar results as "free" ICG (58%; 60 min). A 99m Tc-NanoColl, Pb, and cocktail ICG enriches the standard 99m Tc-NanoColl approach by adding optical detection of the sentinel lymph nodes. Furthermore, this approach improves fluorescent-based guidance and enables both accurate surgical planning and intraoperative detection, based on a single injection. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

The aim of the current narrative review was to summarize the available evidence in the literature on artificial intelligence (AI) methods that have been applied during robotic surgery. Methods A narrative review of the literature was performed on MEDLINE/Pubmed and Scopus database on the topics of artificial intelligence, autonomous surgery, machine learning, robotic surgery, and surgical navigation, focusing on articles published between January 2015 and June 2019. All available evidences were analyzed and summarized herein after an interactive peer-review process of the panel.