Effectiveness of Functionalized Nanosystems for Multimodal Molecular Sensing and Imaging in Medicine

Abstract

Successful employment of multimodal molecular imaging for cancer targeting entails the development of safe nanoparticle contrast agents (NPCAs), detects at least by two nonionizing imaging techniques. This paper presents a quantitative assessment of the effectiveness of both pure silica nanospheres (SiNSs) and composite silica/superparamagnetic NPCAs as scatterers for low-frequency diagnostic ultrasound (US) (3 MHz) in very low range of concentrations (1.5-5 mg/mL). Iron oxide (IO) and FePt-IO nanocrystals are employed for SiNS magnetic coating. Different samples of NPCA-containing agarose gel are US imaged through a commercially available system and acquired data are processed through a dedicated prototypal platform to extract image backscatter information and perform evaluation of the image gray level. The pure silica NPCAs confirms recent reports for higher concentrations at higher frequencies. The FePt-IO-coated NPCAs show similar behavior, although with lower values of image backscatter, with a marked effectiveness peak for 330-nm SiNSs, particularly useful for tumor targeting purposes. Finally, the IO-coated SiNSs presented a marked lowering of US enhancement potential and a peak efficiency for a particle diameter of 660 nm. The extent of US backscatter reduction is found to be a function of the number of magnetic nanoparticles per mL of NPCA-containing gel and decreased with increasing NPCA concentrations. These results broadened our knowledge of dual-mode molecular imaging of deep tumors, employing US, and magnetic resonance techniques for the accurate, safe and early detection of cancer cells located in internal organs.Index Terms-Biomedical cancer detection, biomedical image processing, medical diagnostic imaging molecular imaging, nanoparticles.

Multiparametric Evaluation of the Acoustic Behavior of Halloysite Nanotubes for Medical Echographic Image Enhancement

“…Our results regarding the backscatter signal related to HNTs identified level of enhancement levels comparable to those obtained with other nanoparticle contrast agent under similar experimental conditions [11], [14], [15], although direct terms of comparison with other HNT based research studies are still unavailable due to the relatively recent popularity HNT are experiencing for clinical applications.…”

“…Conversely to those nanoparticle contrast agents characterized by geometrical symmetry [11], [14], [15], the elongated structure and the nonhomogeneous length of the HNTs may cause such nonlinearity of their acoustic behavior, although the analysis of a large population of frames and the realization of triplicate samples for each concentration aimed to reduce the effect of such anisotropies on the backscatter signals. Therefore, among the studied concentrations, 3 mg/mL could rather represent the critical value at which the US signal attenuation, due to the shielding by HNTs included in the phantoms, balances the US enhancement; on the other hand, the shielding effect appeared overcome when the highest concentration is employed with a signal increment between 3 and 5 mg/mL lower than that registered between 0 and 1.5 mg/mL.…”

“…Since the HNTs were polydisperse length of 0.5 to 2 µm [4] (40-50, 15-20-nm diameter of the empty lumen), the adopted amount of HNTs were quantified in mg/mL and corresponded to 1.5, 3, and 5 mg of HNT in 1 mL of agarose gel. These concentrations were chosen, according to a previously validated frame of analysis [15], [16] and three samples were obtained for each examined HNT concentration. The setup includes: 1) a commercial clinically available digital echograph (MyLab XVG, Esaote Spa, Genoa, Italy) connected to a linear echographic transducer (LA523, Esaote Spa, Genoa, Italy); 2) a platform for the acquisition of raw RF signals digitized at 50 MHz, 16 bit (FEMMINA system, ELEN Spa, Florence, Italy) [17] linked to the echograph by means of an optical fiber (1 Gb/s); 3) a water thank equipped, at the bottom, with a support to perpendicularly hold the Eppendorf; 4) a motorized mechanism of an infusion pump (KDS 100, KD Scientific Inc., Holliston, MA), on which the US probe was mounted to perform automatic and repeatable phantom scanning.…”

Assessment of the enhancement potential of Halloysite Nanotubes for echographic imaging

“…Subsequently, the desired amount of HNTs (purified dehydrated HNTs were obtained from Applied Minerals, Inc) were added to agarose solution in a vial, and the mixture was sonicated for 30 seconds; 1 mL of the obtained suspension was quickly poured into the Eppendorf tube. Since the majority of the HNTs consists of cylindrical tubes of 40-50 nm diameter and length of 0.5 to 2 µm polydisperse in length, empty lumen of the halloysite with 15-20 nm diameters [4], the adopted amount of HNTs were quantified in mg/mL and corresponded to 1.5, 3 and 5 mg of HNT in 1 mL of agarose gel, according to a previously validated frame of analysis [11], [12]. Three samples were obtained for each examined HNT concentration.…”

Laser fluence and exposure time effects on optoacoustic signal from gold nanorods for enhanced medical imaging

“…However, specifically where the nanoparticle (NP) can extravasate [15]; thus specific functionalization should be tailored [16] upon the study of the NP toxicity profile, as reported in literature for other nanostructured compounds [17]. In most cases gold is the metal of choice for NP manufacturing and the use of gold NP as diagnostic probes has also been demonstrated feasible by preliminary murine studies [18], [19].…”