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

Design principles for noninvasive, longitudinal and quantitative cell tracking with nanoparticle-based CT imaging

Contradictory results in clinical trials are preventing the advancement and implementation of cell-based therapy. To explain such results, there is a need to uncover the mystery regarding the fate of the transplanted cells. To answer this need, we developed a technique for noninvasive in vivo cell tracking, which uses gold nanoparticles as contrast agents for CT imaging. Herein, we investigate the design principles of this technique for intramuscular transplantation of therapeutic cells. Longitudinal studies were performed, displaying the ability to track cells over long periods of time. As few as 500 cells could be detected and a way to quantify the number of cells visualized by CT was demonstrated. Moreover, monitoring of cell functionality was demonstrated on a mouse model of Duchenne muscular dystrophy. This cell-tracking technology has the potential to become an essential tool in pre-clinical as well as clinical trials and to advance the future of cell therapy

Therapeutic Effect of Astroglia-like Mesenchymal Stem Cells Expressing Glutamate Transporter in a Genetic Rat Model of Depression

Recent studies have proposed that abnormal glutamatergic neurotransmission and glial pathology play an important role in the etiology and manifestation of depression. It was postulated that restoration of normal glutamatergic transmission, by enhancing glutamate uptake, may have a beneficial effect on depression. We examined this hypothesis using unique human glial-like mesenchymal stem cells (MSCs), which in addition to inherent properties of migration to regions of injury and secretion of neurotrophic factors, were differentiated to express high levels of functional glutamate transporters (excitatory amino acid transporters; EAAT). Additionally, gold nanoparticles (GNPs), which serve as contrast agents for CT imaging, were loaded into the cells for non-invasive, real-time imaging and tracking of MSC migration and final location within the brain. MSC-EAAT (2×105; 10 μl) were administered (i.c.v.) to Flinder Sensitive Line rats (FSLs), a genetic model for depression, and longitudinal behavioral and molecular changes were monitored. FSL rats treated with MSC-EAAT showed attenuated depressive-like behaviors (measured by the forced swim test, novelty exploration test and sucrose self-administration paradigm), as compared to controls. CT imaging, Flame Atomic Absorption Spectroscopy analysis and immunohistochemistry showed that the majority of MSCs homed specifically to the dentate gyrus of the hippocampus, a region showing structural brain changes in depression, including loss of glial cells. mRNA and protein levels of EAAT1 and BDNF were significantly elevated in the hippocampus of MSC-EAAT-treated FSLs. Our findings indicate that MSC-EAATs effectively improve depressive-like manifestations, possibly in part by increasing both glutamate uptake and neurotropic factor secretion in the hippocampus

Placenta-Derived Mesenchymal-like Adherent Stromal Cells as an Effective Cell Therapy for Cocaine Addiction in a Rat Model

Recent research points to mesenchymal stem cells’ potential for treating neurological disorders, especially drug addiction. We examined the longitudinal effect of placenta-derived mesenchymal stromal-like cells (PLX-PAD) in a rat model for cocaine addiction. Sprague–Dawley male rats were trained to self-administer cocaine or saline daily until stable maintenance. Before the extinction phase, PLX-PAD cells were administered by intracerebroventricular or intranasal routes. Neurogenesis was evaluated, as was behavioral monitoring for craving. We labeled the PLX-PAD cells with gold nanoparticles and followed their longitudinal migration in the brain parallel to their infiltration of essential peripheral organs both by micro-CT and by inductively coupled plasma-optical emission spectrometry. Cell locations in the brain were confirmed by immunohistochemistry. We found that PLX-PAD cells attenuated cocaine-seeking behavior through their capacity to migrate to specific mesolimbic regions, homed on the parenchyma in the dentate gyrus of the hippocampus, and restored neurogenesis. We believe that intranasal cell therapy is a safe and effective approach to treating addiction and may offer a novel and efficient approach to rehabilitation

Differentiating Between Cancer and Inflammation: A Metabolic-Based Method for Functional Computed Tomography Imaging

One of the main limitations of the highly used cancer imaging technique, PET-CT, is its inability to distinguish between cancerous lesions and post treatment inflammatory conditions. The reason for this lack of specificity is that [¹⁸F]­FDG-PET is based on increased glucose metabolic activity, which characterizes both cancerous tissues and inflammatory cells. To overcome this limitation, we developed a nanoparticle-based approach, utilizing glucose-functionalized gold nanoparticles (GF-GNPs) as a metabolically targeted CT contrast agent. Our approach demonstrates specific tumor targeting and has successfully distinguished between cancer and inflammatory processes in a combined tumor-inflammation mouse model, due to dissimilarities in angiogenesis occurring under different pathologic conditions. This study provides a set of capabilities in cancer detection, staging and follow-up, and can be applicable to a wide range of cancers that exhibit high metabolic activity

Nanomedicine for Cancer Immunotherapy: Tracking Cancer-Specific T‑Cells <i>in Vivo</i> with Gold Nanoparticles and CT Imaging

Application of immune cell-based therapy in routine clinical practice is challenging due to the poorly understood mechanisms underlying success or failure of treatment. Development of accurate and quantitative imaging techniques for noninvasive cell tracking can provide essential knowledge for elucidating these mechanisms. We designed a novel method for longitudinal and quantitative <i>in vivo</i> cell tracking, based on the superior visualization abilities of classical X-ray computed tomography (CT), combined with state-of-the-art nanotechnology. Herein, T-cells were transduced to express a melanoma-specific T-cell receptor and then labeled with gold nanoparticles (GNPs) as a CT contrast agent. The GNP-labeled T-cells were injected intravenously to mice bearing human melanoma xenografts, and whole-body CT imaging allowed examination of the distribution, migration, and kinetics of T-cells. Using CT, we found that transduced T-cells accumulated at the tumor site, as opposed to nontransduced cells. Labeling with gold nanoparticles did not affect T-cell function, as demonstrated both <i>in vitro</i>, by cytokine release and proliferation assays, and <i>in vivo</i>, as tumor regression was observed. Moreover, to validate the accuracy and reliability of the proposed cell tracking technique, T-cells were labeled both with green fluorescent protein for fluorescence imaging, and with GNPs for CT imaging. A remarkable correlation in signal intensity at the tumor site was observed between the two imaging modalities, at all time points examined, providing evidence for the accuracy of our CT cell tracking abilities. This new method for cell tracking with CT offers a valuable tool for research, and more importantly for clinical applications, to study the fate of immune cells in cancer immunotherapy