A new method for cancer detection based on diffusion reflection measurements of targeted gold nanorods

This paper presents a new method for cancer detection based on diffusion reflection measurements. This method enables discrimination between cancerous and noncancerous tissues due to the intense light absorption of gold nanorods (GNRs), which are selectively targeted to squamous cell carcinoma head and neck cancer cells. Presented in this paper are tissue-like phantom and in vivo results that demonstrate the high sensitivity of diffusion reflection measurements to the absorption differences between the GNR-targeted cancerous tissue and normal, noncancerous tissue. This noninvasive and nonionizing optical detection method provides a highly sensitive, simple, and inexpensive tool for cancer detection

Targeted gold nanoparticles enable molecular CT imaging of cancer: an in vivo study

In recent years, advances in molecular biology and cancer research have led to the identification of sensitive and specific biomarkers that associate with various types of cancer. However, in vivo cancer detection methods with computed tomography, based on tracing and detection of these molecular cancer markers, are unavailable today. This paper demonstrates in vivo the feasibility of cancer diagnosis based on molecular markers rather than on anatomical structures, using clinical computed tomography. Anti-epidermal growth factor receptor conjugated gold nanoparticles (30 nm) were intravenously injected into nude mice implanted with human squamous cell carcinoma head and neck cancer. The results clearly demonstrate that a small tumor, which is currently undetectable through anatomical computed tomography, is enhanced and becomes clearly visible by the molecularly-targeted gold nanoparticles. It is further shown that active tumor targeting is more efficient and specific than passive targeting. This noninvasive and nonionizing molecular cancer imaging tool can facilitate early cancer detection and can provide researchers with a new technique to investigate in vivo the expression and activity of cancer-related biomarkers and molecular processes

The effect of nanoparticle size on the probability to cross the blood-brain barrier: an in-vitro endothelial cell model

BACKGROUND: During the last decade nanoparticles have gained attention as promising drug delivery agents that can transport through the blood brain barrier. Recently, several studies have demonstrated that specifically targeted nanoparticles which carry a large payload of therapeutic agents can effectively enhance therapeutic agent delivery to the brain. However, it is difficult to draw definite design principles across these studies, owing to the differences in material, size, shape and targeting agents of the nanoparticles. Therefore, the main objective of this study is to develop general design principles that link the size of the nanoparticle with the probability to cross the blood brain barrier. Specifically, we investigate the effect of the nanoparticle size on the probability of barbiturate coated GNPs to cross the blood brain barrier by using bEnd.3 brain endothelial cells as an in vitro blood brain barrier model. RESULTS: The results show that GNPs of size 70 nm are optimal for the maximum amount of gold within the brain cells, and that 20 nm GNPs are the optimal size for maximum free surface area. CONCLUSIONS: These findings can help understand the effect of particle size on the ability to cross the blood brain barrier through the endothelial cell model, and design nanoparticles for brain imaging/therapy contrast agents.Israel Cancer Research Fund (ICRF), Teva Pharmaceutical Industries Ltd

Theranostic Approach for Cancer Treatment: Multifunctional Gold Nanorods for Optical Imaging and Photothermal Therapy

A critical problem in the treatment of cancer is the inability to identify microsized tumors and treat them without normal tissue destruction. While surgical excision of tumors is highly effective, residual micrometastases and remaining positive margins are the main cause of recurrence. In this study, we propose a theranostic approach for the detection and therapy of head and neck cancer (HNC). We developed a plasmonic-based nanoplatform for combined, ultrasensitive in vivo spectroscopic detection and targeted therapy of HNC. This detection method involves near-infrared (NIR) spectroscopy of gold nanorods (GNRs) that selectively target and attach to squamous cell carcinoma HNC cells, through an immune complex. Diagnosis is based on a spectral shift analysis, which is generated by interparticle-plasmon-resonance patterns of the specifically targeted GNRs. Additionally, the ability to design the GNRs to strongly absorb light in the NIR region enables efficient irradiation of these GNRs, for selective photothermal therapy (PTT) of the cancer cells. We expect this targeted, noninvasive, and nonionizing spectroscopic detection method to provide a highly sensitive and simple diagnostic tool for micrometastasis. In addition, the concomitant development of targeted PTT, based on specific cancer markers, may pave the way for tailoring effective therapy for patients, toward an era of personalized medicine

Theranostic Approach for Cancer Treatment: Multifunctional Gold Nanorods for Optical Imaging and Photothermal Therapy

A critical problem in the treatment of cancer is the inability to identify microsized tumors and treat them without normal tissue destruction. While surgical excision of tumors is highly effective, residual micrometastases and remaining positive margins are the main cause of recurrence. In this study, we propose a theranostic approach for the detection and therapy of head and neck cancer (HNC). We developed a plasmonic-based nanoplatform for combined, ultrasensitive in vivo spectroscopic detection and targeted therapy of HNC. This detection method involves near-infrared (NIR) spectroscopy of gold nanorods (GNRs) that selectively target and attach to squamous cell carcinoma HNC cells, through an immune complex. Diagnosis is based on a spectral shift analysis, which is generated by interparticle-plasmon-resonance patterns of the specifically targeted GNRs. Additionally, the ability to design the GNRs to strongly absorb light in the NIR region enables efficient irradiation of these GNRs, for selective photothermal therapy (PTT) of the cancer cells. We expect this targeted, noninvasive, and nonionizing spectroscopic detection method to provide a highly sensitive and simple diagnostic tool for micrometastasis. In addition, the concomitant development of targeted PTT, based on specific cancer markers, may pave the way for tailoring effective therapy for patients, toward an era of personalized medicine

Au nanodyes as enhanced contrast agents in wide field near infrared fluorescence lifetime imaging

Abstract The near-infrared (NIR) range of the electromagnetic (EM) spectrum offers a nearly transparent window for imaging tissue. Despite the significant potential of NIR fluorescence-based imaging, its establishment in basic research and clinical applications remains limited due to the scarcity of fluorescent molecules with absorption and emission properties in the NIR region, especially those suitable for biological applications. In this study, we present a novel approach by combining the widely used IRdye 800NHS fluorophore with gold nanospheres (GNSs) and gold nanorods (GNRs) to create Au nanodyes, with improved quantum yield (QY) and distinct lifetimes. These nanodyes exhibit varying photophysical properties due to the differences in the separation distance between the dye and the gold nanoparticles (GNP). Leveraging a rapid and highly sensitive wide-field fluorescence lifetime imaging (FLI) macroscopic set up, along with phasor based analysis, we introduce multiplexing capabilities for the Au nanodyes. Our approach showcases the ability to differentiate between NIR dyes with very similar, short lifetimes within a single image, using the combination of Au nanodyes and wide-field FLI. Furthermore, we demonstrate the uptake of Au nanodyes by mineral-oil induced plasmacytomas (MOPC315.bm) cells, indicating their potential for in vitro and in vivo applications. Graphical abstrac

Phosphate-Trapping Liposomes for Long-Term Management of Hyperphosphatemia

Hyperphosphatemia is a typical complication of end-stage renal disease, characterized by elevated and life-threatening serum phosphate levels. Hemodialysis does not enable sufficient clearance of phosphate, due to slow cell-to-plasma kinetics of phosphate ions; moreover, dietary restrictions and conventional treatment with oral phosphate binders have low success rates, together with adverse effects. Here, we developed a new concept of phosphate-trapping liposomes, to improve and prolong the control over serum phosphate levels. We designed liposomes modified with polyethylene glycol and encapsulated with the phosphate binder ferric citrate (FC liposomes). These liposomes were found to trap phosphate ions in their inner core, and thereby lower free phosphate ion concentrations in solution and in serum. The FC liposomes showed higher phosphate binding ability as phosphate concentrations increased. Moreover, these liposomes showed a time-dependent increase in uptake of phosphate, up to 25 h in serum. Thus, our findings demonstrate effective long-term phosphate trapping by FC liposomes, indicating their potential to reduce serum phosphate toxicity and improve current management of hyperphosphatemia