Noninvasive photoacoustic sentinel lymph node mapping using Au nanocages as a lymph node tracer in a rat model

Sentinel lymph node biopsy (SLNB) has been widely performed and become the standard procedure for axillary staging in breast cancer patients. In current SLNB, identification of SLNs is prerequisite, and blue dye and/or radioactive colloids are clinically used for mapping. However, these methods are still intraoperative, and especially radioactive colloids based method is ionizing. As a result, SLNB is generally associated with ill side effects. In this study, we have proposed near-infrared Au nanocages as a new tracer for noninvasive and nonionizing photoacoustic (PA) SLN mapping in a rat model as a step toward clinical applications. Au nanocages have great features: biocompatibility, easy surface modification for biomarker, a tunable surface plasmon resonance (SPR) which allows for peak absorption to be optimized for the laser being used, and capsule-type drug delivery. Au nanocage-enhanced photoacoustic imaging has the potential to be adjunctive to current invasive SLNB for preoperative axillary staging in breast cancer patients

Near-Infrared Gold Nanocages as a New Class of Tracers for Photoacoustic Sentinel Lymph Node Mapping on a Rat Model

This work demonstrated the use of Au nanocages as a new class of lymph node tracers for noninvasive photoacoustic (PA) imaging of a sentinel lymph node (SLN). Current SLN mapping methods based on blue dye and/or nanometer-sized radioactive colloid injection are intraoperative due to the need for visual detection of the blue dye and low spatial resolution of Geiger counters in detecting radioactive colloids. Compared to the current methods, PA mapping based on Au nanocages shows a number of attractive features: noninvasiveness, strong optical absorption in the near-infrared region (for deep penetration), and the accumulation of Au nanocages with a higher concentration than the initial solution for the injection. In an animal model, these features allowed us to identify SLNs containing Au nanocages as deep as 33 mm below the skin surface with good contrast. Most importantly, compared to methylene blue Au nanocages can be easily bioconjugated with antibodies for targeting specific receptors, potentially eliminating the need for invasive axillary staging procedures in addition to providing noninvasive SLN mapping

Near-Infrared Gold Nanocages as a New Class of Tracers for Photoacoustic Sentinel Lymph Node Mapping on a Rat Model

This work demonstrated the use of Au nanocages as a new class of lymph node tracers for noninvasive photoacoustic (PA) imaging of a sentinel lymph node (SLN). Current SLN mapping methods based on blue dye and/or nanometer-sized radioactive colloid injection are intraoperative due to the need for visual detection of the blue dye and low spatial resolution of Geiger counters in detecting radioactive colloids. Compared to the current methods, PA mapping based on Au nanocages shows a number of attractive features: noninvasiveness, strong optical absorption in the near-infrared region (for deep penetration), and the accumulation of Au nanocages with a higher concentration than the initial solution for the injection. In an animal model, these features allowed us to identify SLNs containing Au nanocages as deep as 33 mm below the skin surface with good contrast. Most importantly, compared to methylene blue Au nanocages can be easily bioconjugated with antibodies for targeting specific receptors, potentially eliminating the need for invasive axillary staging procedures in addition to providing noninvasive SLN mapping

Noninvasive photoacoustic sentinel lymph node mapping using Au nanocages as a lymph node tracer in a rat model

Sentinel lymph node biopsy (SLNB) has been widely performed and become the standard procedure for axillary staging in breast cancer patients. In current SLNB, identification of SLNs is prerequisite, and blue dye and/or radioactive colloids are clinically used for mapping. However, these methods are still intraoperative, and especially radioactive colloids based method is ionizing. As a result, SLNB is generally associated with ill side effects. In this study, we have proposed near-infrared Au nanocages as a new tracer for noninvasive and nonionizing photoacoustic (PA) SLN mapping in a rat model as a step toward clinical applications. Au nanocages have great features: biocompatibility, easy surface modification for biomarker, a tunable surface plasmon resonance (SPR) which allows for peak absorption to be optimized for the laser being used, and capsule-type drug delivery. Au nanocage-enhanced photoacoustic imaging has the potential to be adjunctive to current invasive SLNB for preoperative axillary staging in breast cancer patients

Measuring the Optical Absorption Cross Sections of Au−Ag Nanocages and Au Nanorods by Photoacoustic Imaging

This paper presents a method for measuring the optical absorption cross sections (σ_a) of Au−Ag nanocages and Au nanorods. The method is based on photoacoustic (PA) imaging, where the detected signal is directly proportional to the absorption coefficient (μ_a) of the nanostructure. For each type of nanostructure, we first obtained μ_a from the PA signal by benchmarking against a linear calibration curve (PA signal versus μ_a) derived from a set of methylene blue solutions with different concentrations. We then calculated σ_a by dividing the μ_a by the corresponding concentration of the Au nanostructure. Additionally, we obtained the extinction cross section (σ_e, sum of absorption and scattering) from the extinction spectrum recorded using a conventional UV−vis−NIR spectrometer. From the measurements of σ_a and σ_e, we were able to easily derive both the absorption and scattering cross sections for each type of gold nanostructure. The ratios of absorption to extinction obtained from experimental and theoretical approaches agreed well, demonstrating the potential use of this method in determining the optical absorption and scattering properties of gold nanostructures and other types of nanomaterials

Photoacoustic quantification of the optical absorption cross-sections of gold nanostructures

This study demonstrates a method for measuring the optical absorption cross-sections (σ_a) of Au-Ag nanocages and Au nanorods using photoacoustic (PA) sensing. PA signals are directly proportional to the absorption coefficient (μ_a) of the nanostructure. For each type of nanostructure, we first obtained μa from the PA signal by benchmarking against a linear calibration curve (PA signal vs. μ_a) derived from a set of methylene blue solutions with different concentrations. We then calculated σ_a by dividing the μ_a by the corresponding concentration of the Au nanostructure. Additionally, we obtained the extinction cross-section (σ_e, sum of absorption and scattering cross-sections) from the extinction spectrum recorded using a conventional UV-vis-NIR spectrometer. From the measurements of σ_a and σ_e, we were able to easily derive both the absorption and scattering cross-sections for each type of gold nanostructure. This method can potentially provide the optical absorption and scattering properties of gold nanostructures and other types of nanomaterials

Reply to Comment on Conopeptide-Functionalized Nanoparticles Selectively Antagonize Extrasynaptic N-Methyl-d-aspartate Receptors and Protect Hippocampal Neurons from Excitotoxicity In Vitro

In this manuscript, we provide precise answers to the concerns expressed by Molokanova et al. in their comment. In our reply, we highlight that there is indeed substantial agreement between our study and the one reported in Nano Letters by the Molokanova’s group.1 We believe this is a very important aspect because it proves the validity of the chosen approach, i.e. PEGylated AuNPs carrying NMDAR antagonists and with an overall dimension large enough to prevent their diffusion into the synapse can exclusively antagonize extrasynaptic NMDAR-mediated currents and are thereby neuroprotective

Gold nanocages covered by smart polymers for controlled release with near-infrared light

Photosensitive caged compounds have enhanced our ability to address the complexity of biological systems by generating effectors with remarkable spatial/temporal resolutions. The caging effect is typically removed by photolysis with ultraviolet light to liberate the bioactive species. Although this technique has been successfully applied to many biological problems, it suffers from a number of intrinsic drawbacks. For example, it requires dedicated efforts to design and synthesize a precursor compound for each effector. The ultraviolet light may cause damage to biological samples and is suitable only for in vitro studies because of its quick attenuation in tissue. Here we address these issues by developing a platform based on the photothermal effect of gold nanocages. Gold nanocages represent a class of nanostructures with hollow interiors and porous walls. They can have strong absorption (for the photothermal effect) in the near-infrared while maintaining a compact size. When the surface of a gold nanocage is covered with a smart polymer, the pre-loaded effector can be released in a controllable fashion using a near-infrared laser. This system works well with various effectors without involving sophisticated syntheses, and is well suited for in vivo studies owing to the high transparency of soft tissue in the near-infrared region

Measuring the Optical Absorption Cross Sections of Au−Ag Nanocages and Au Nanorods by Photoacoustic Imaging

This paper presents a method for measuring the optical absorption cross sections (σ_a) of Au−Ag nanocages and Au nanorods. The method is based on photoacoustic (PA) imaging, where the detected signal is directly proportional to the absorption coefficient (μ_a) of the nanostructure. For each type of nanostructure, we first obtained μ_a from the PA signal by benchmarking against a linear calibration curve (PA signal versus μ_a) derived from a set of methylene blue solutions with different concentrations. We then calculated σ_a by dividing the μ_a by the corresponding concentration of the Au nanostructure. Additionally, we obtained the extinction cross section (σ_e, sum of absorption and scattering) from the extinction spectrum recorded using a conventional UV−vis−NIR spectrometer. From the measurements of σ_a and σ_e, we were able to easily derive both the absorption and scattering cross sections for each type of gold nanostructure. The ratios of absorption to extinction obtained from experimental and theoretical approaches agreed well, demonstrating the potential use of this method in determining the optical absorption and scattering properties of gold nanostructures and other types of nanomaterials