Optical Drug Monitoring: Photoacoustic Imaging of Nanosensors to Monitor Therapeutic Lithium in Vivo

Personalized medicine could revolutionize how primary care physicians treat chronic disease and how researchers study fundamental biological questions. To realize this goal, we need to develop more robust, modular tools and imaging approaches for in vivo monitoring of analytes. In this report, we demonstrate that synthetic nanosensors can measure physiologic parameters with photoacoustic contrast, and we apply that platform to continuously track lithium levels in vivo. Photoacoustic imaging achieves imaging depths that are unattainable with fluorescence or multiphoton microscopy. We validated the photoacoustic results that illustrate the superior imaging depth and quality of photoacoustic imaging with optical measurements. This powerful combination of techniques will unlock the ability to measure analyte changes in deep tissue and will open up photoacoustic imaging as a diagnostic tool for continuous physiological tracking of a wide range of analytes

Inulin coated plasmonic gold nanoparticles as a tumor-selective tool for cancer therapy

Polymer coated gold nanospheres are proposed as a tumor selective carrier for the anticancer drug doxorubicin. Thiolated polyethyleneglycol (PEG-SH) and an inulin-amino derivative based copolymer (INU-EDA) were used as stabilizing and coating materials for 40 nm gold nanospheres. The resulting polymer coated gold nanospheres (Au@PEG-INU) showed excellent physicochemical stability and potential stealth like behavior. The system was loaded with doxorubicin (Au@PEG-INU/Doxo) and its cytotoxicity profile was evaluated on human cervical cancer cells (HeLa) and lung cancer cells (A549), as compared to Au@PEG-INU and doxorubicin alone. Cytotoxicity assays showed that the system is able to drastically reduce cell viability upon incubation for 3 days. This result was supported by the ability of Au@PEG-INU/Doxo to be internalized by cancer cells and to release doxorubicin, as assessed by fluorescence microscopy. Finally, a cancer/non cancer cell co-culture model was used to display the advantageous therapeutic effects of the proposed system with respect to doxorubicin alone, thereby demonstrating the ability of Au@PEG-INU/Doxo to preferentially accumulate in tumor cells due to their enhanced metabolism, and to selectively kill target cells

Present and Future of Surface Enhanced Raman Scattering

The discovery of the enhancement of Raman scattering by molecules adsorbed on nanostructured metal surfaces is a landmark in the history of spectroscopic and analytical techniques. Significant experimental and theoretical effort has been directed toward under standing the surface-enhanced Raman scattering (SERS) effect and demonstrating its potential in various types of ultrasensitive sensing applications in a wide variety of fields. In the 45 years since its discovery, SERS has blossomed into a rich area of research and technology, but additional efforts are still needed before it can be routinely used analytically and in commercial products. In this Review, prominent authors from around the world joined together to summarize the state of the art in understanding and using SERS and to predict what can be expected in the near future in terms of research, applications, and technological development. This Review is dedicated to SERS pioneer and our coauthor, the late Prof. Richard Van Duyne, whom we lost during the preparation of this article

SERSTEM: An app for the statistical analysis of correlative SERS and TEM imaging and evaluation of SERS tags performance

Raman spectroscopy is becoming increasingly popular as an in vitro bioimaging technique, when coupled with plasmonic substrates such as gold nanoparticles (AuNPs). Plasmonic AuNPs not only display excellent biocompatibility but can also induce the surface-enhanced Raman scattering (SERS) effect, which can be exploited for cell labeling, as an interesting alternative to fluorescence-based techniques. SERS bioimaging requires the use of so-called SERS tags or SERS-encoded AuNPs. A remaining difficulty toward the general implementation of this method is the difficulty to correlate the SERS signal (spectral intensity) with the number of SERS tags. Therefore, a general correlation method, suitable for arbitrary AuNP morphologies and Raman-active molecules (Raman reporters or RaRs), should largely improve the quantitative character of SERS as an imaging technique. We propose a protocol, with an associated app (SERSTEM), which enables the user to determine the average SERS intensity per nanoparticle from transmission electron microscopy (TEM) and SERS data. As a proof of concept, we demonstrated the method for Au nanostars and nanorods, carrying four different RaRs, and implemented the SERSTEM app, which is publicly available from an open-source platform

Modeling nanoparticle–alveolar epithelial cell interactions under breathing conditions using captive bubble surfactometry

Many advances have been made in recent years in cell culture models of the epithelial barrier of the lung from simple monolayers to complex 3-D systems employing different cell types. However, the vast majority of these models still present a static air–liquid interface which is unrealistic given the dynamic nature of breathing. We present here a method where epithelial lung cells are integrated into a system, the captive bubble surfactometer, which allows the cyclical compression and expansion of the surfactant film at the air–liquid interface, thus modeling the dynamics of breathing. We found that cellular uptake of deposited gold nanoparticles was significantly increased under the dynamic (breathing) conditions of compression and expansion as compared to static conditions. The method could be very useful for studying nanoparticle–alveolar lung cell interactions under breathing conditions for applications in nanomedicine and toxicology

Modeling Nanoparticle–Alveolar Epithelial Cell Interactions under Breathing Conditions Using Captive Bubble Surfactometry

Many advances have been made in recent years in cell culture models of the epithelial barrier of the lung from simple monolayers to complex 3-D systems employing different cell types. However, the vast majority of these models still present a static air–liquid interface which is unrealistic given the dynamic nature of breathing. We present here a method where epithelial lung cells are integrated into a system, the captive bubble surfactometer, which allows the cyclical compression and expansion of the surfactant film at the air–liquid interface, thus modeling the dynamics of breathing. We found that cellular uptake of deposited gold nanoparticles was significantly increased under the dynamic (breathing) conditions of compression and expansion as compared to static conditions. The method could be very useful for studying nanoparticle–alveolar lung cell interactions under breathing conditions for applications in nanomedicine and toxicology