The changes of CD4+CD25+/CD4+ proportion in spleen of tumor-bearing BALB/c mice

CD4+CD25+ regulatory T lymphocytes (T(R)) constitute 5–10% of peripheral CD4+ T cells in naive mice and humans, and play an important role in controlling immune responses. Accumulating evidences show that T(R )cells are involved in some physiological processes and pathologic conditions such as autoimmune diseases, transplantation tolerance and cancer, and might be a promising therapeutic target for these diseases. To evaluate the change of CD4+CD25+ T(R )cells in mouse tumor models, CD4+CD25+ subset in peripheral blood and spleen lymphocytes from normal or C26 colon-carcinoma-bearing BABL/c mice were analyzed by flow cytometry using double staining with CD4 and CD25 antibodies. The proportion of CD4+CD25+/CD4+ in spleen lymphocytes was found to be higher than that in peripheral blood lymphocytes in normal mice. No difference was observed in the proportion in peripheral blood lymphocytes between tumor bearing mice and normal mice, while there was a significant increase in the proportion in spleen lymphocytes in tumor bearing mice as compared with normal mice. Moreover, the proportion increased in accordance with the increase in the tumor sizes. The increase in the proportion was due to the decrease in CD4+ in lymphocytes, which is resulted from decreased CD4+CD25- subset in lymphocytes. Our observation suggests the CD4+CD25+/CD4+ proportion in spleen lymphocytes might be a sensitive index to evaluate the T(R )in tumor mouse models, and our results provide some information on strategies of antitumor immunotherapy targeting CD4+CD25+ regulatory T lymphocytes

Effect of intra-articular administration of superparamagnetic iron oxide nanoparticles (SPIONs) for MRI assessment of the cartilage barrier in a large animal model

<div><p>Early diagnosis of cartilage disease at a time when changes are limited to depletion of extracellular matrix components represents an important diagnostic target to reduce patient morbidity. This report is to present proof of concept for nanoparticle dependent cartilage barrier imaging in a large animal model including the use of clinical magnetic resonance imaging (MRI). Conditioned (following matrix depletion) and unconditioned porcine metacarpophalangeal cartilage was evaluated on the basis of fluorophore conjugated 30 nm and 80 nm spherical gold nanoparticle permeation and multiphoton laser scanning and bright field microscopy after autometallographic particle enhancement. Consequently, conditioned and unconditioned joints underwent MRI pre- and post-injection with 12 nm superparamagnetic iron oxide nanoparticles (SPIONs) to evaluate particle permeation in the context of matrix depletion and use of a clinical 1.5 Tesla MRI scanner. To gauge the potential pro-inflammatory effect of intra-articular nanoparticle delivery co-cultures of equine synovium and cartilage tissue were exposed to an escalating dose of SPIONs and IL-6, IL-10, IFN-γ and PGE₂ were assessed in culture media. The chemotactic potential of growth media samples was subsequently assessed in transwell migration assays on isolated equine neutrophils. Results demonstrate an increase in MRI signal following conditioning of porcine joints which suggests that nanoparticle dependent compositional cartilage imaging is feasible. Tissue culture and neutrophil migration assays highlight a dose dependent inflammatory response following SPION exposure which at the imaging dose investigated was not different from controls. The preliminary safety and imaging data support the continued investigation of nanoparticle dependent compositional cartilage imaging. To our knowledge, this is the first report in using SPIONs as intra-articular MRI contrast agent for studying cartilage barrier function, which could potentially lead to a new diagnostic technique for early detection of cartilage disease.</p></div

Gold nanocages covered with thermally-responsive polymers for controlled release by high-intensity focused ultrasound

This paper describes the use of Au nanocages covered with smart, thermally-responsive polymers for controlled release with high-intensity focused ultrasound (HIFU). HIFU is a highly precise medical procedure that uses focused ultrasound to heat and destroy pathogenic tissue rapidly and locally in a non-invasive or minimally invasive manner. The released dosage could be remotely controlled by manipulating the power of HIFU and/or the duration of exposure. We demonstrated localized release within the focal volume of HIFU by using gelatin phantom samples containing dye-loaded Au nanocages. By placing chicken breast tissues on top of the phantoms, we further demonstrated the feasibility of this system for controlled release at depths up to 30 mm. Because it can penetrate more deeply into soft tissues than near-infrared light, HIFU is a potentially more effective external stimulus for rapid, on-demand drug release

A fiber optoacoustic guide with augmented reality for precision breast-conserving surgery

Lumpectomy, also called breast-conserving surgery, has become the standard surgical treatment for early-stage breast cancer. However, accurately locating the tumor during a lumpectomy, especially when the lesion is small and nonpalpable, is a challenge. Such difficulty can lead to either incomplete tumor removal or prolonged surgical time, which result in high re-operation rates (~25%) and increased surgical costs. Here, we report a fiber optoacoustic guide (FOG) with augmented reality (AR) for sub-millimeter tumor localization and intuitive surgical guidance with minimal interference. The FOG is preoperatively implanted in the tumor. Under external pulsed light excitation, the FOG omnidirectionally broadcasts acoustic waves through the optoacoustic effect by a specially designed nano-composite layer at its tip. By capturing the acoustic wave, three ultrasound sensors on the breast skin triangulate the FOG tip's position with 0.25-mm accuracy. An AR system with a tablet measures the coordinates of the ultrasound sensors and transforms the FOG tip's position into visual feedback with <1-mm accuracy, thus aiding surgeons in directly visualizing the tumor location and performing fast and accurate tumor removal. We further show the use of a head-mounted display to visualize the same information in the surgeons' first-person view and achieve hands-free guidance. Towards clinical application, a surgeon successfully deployed the FOG to excise a "pseudo tumor" in a female human cadaver. With the high-accuracy tumor localization by FOG and the intuitive surgical guidance by AR, the surgeon performed accurate and fast tumor removal, which will significantly reduce re-operation rates and shorten the surgery time