A novel theranostic gold nanorods- and adriamycin-loaded micelle for EpCA M targeting, laser ablation, and photoacoustic imaging of cancer stem cells in hepatocellular carcinoma

Introduction and purpose: Cancer stem cells (CSCs) present a higher capacity to evade being killed by cancer agents and developing chemoresistance, thus leading to failure of conventional anticancer therapeutics. Nanomaterials specifically designed for targeting and treating not only tumor cells, but also CSCs, may encompass therapeutic and diagnostic tools, thus successfully eradicating the tumor. Materials and methods: Polymeric micelles simultaneously loaded with gold nanorods (GNRs) and Adriamycin were prepared and used as a novel therapeutic and diagnostic weapon. Epithelial cell adhesion molecule (EpCAM) is an important CSC surface marker and has been exploited in this work as an active targeting agent. Photoacoustic imaging was applied for GNR individuation and tissue recognition. Results: The nanosystem was demonstrated to be able to elicit effective targeting of cancer cells and cause their killing, in particular under laser ablation. Moreover, ex vivo photoacoustic imaging is able to clearly identify tumor regions thanks to GNR\u2019s contrast. Conclusion: The nanosystem can be considered a powerful and promising theranostic weapon for hepatocellular carcinoma treatment

Alternating block copolymer-based nanoparticles as tools to modulate the loading of multiple chemotherapeutics and imaging probes

Abstract Cancer therapy often relies on the combined action of different molecules to overcome drug resistance and enhance patient outcome. Combined strategies relying on molecules with different pharmacokinetics often fail due to the lack of concomitant tumor accumulation and, thus, to the loss of synergistic effect. Due to their ability to enhance treatment efficiency, improve drug pharmacokinetics, and reduce adverse effects, polymer nanoparticles (PNPs) have been widely investigated as co-delivery vehicles for cancer therapies. However, co-encapsulation of different drugs and probes in PNPs requires a flexible polymer platform and a tailored particle design, in which both the bulk and surface properties of the carriers are carefully controlled. In this work, we propose a core-shell PNP design based on a polyurethane (PUR) core and a phospholipid external surface. The modulation of the hydrophilic/hydrophobic balance of the PUR core enhanced the encapsulation of two chemotherapeutics with dramatically different water solubility (Doxorubicin hydrochloride, DOXO and Docetaxel, DCTXL) and of Iron Oxide Nanoparticles for MRI imaging. The outer shell remained unchanged among the platforms, resulting in un-modified cellular uptake and in vivo biodistribution. We demonstrate that the choice of PUR core allowed a high entrapment efficiency of all drugs, superior or comparable to previously reported results, and that higher core hydrophilicity enhances the loading efficiency of the hydrophilic DOXO and the MRI contrast effect. Moreover, we show that changing the PUR core did not alter the surface properties of the carriers, since all particles showed a similar behavior in terms of cell internalization and in vivo biodistribution. We also show that PUR PNPs have high passive tumor accumulation and that they can efficient co-deliver the two drugs to the tumor, reaching an 11-fold higher DOXO/DCTXL ratio in tumor as compared to free drugs. Statement of Significance Exploiting the synergistic action of multiple chemotherapeutics is a promising strategy to improve the outcome of cancer patients, as different agents can simultaneously engage different features of tumor cells and/or their microenvironment. Unfortunately, the choice is limited to drugs with similar pharmacokinetics that can concomitantly accumulate in tumors. To expand the spectrum of agents that can be delivered in combination, we propose a multi-compartmental core-shell nanoparticles approach, in which the core is made of biomaterials with high affinity for drugs of different physical properties. We successfully co-encapsulated Doxorubicin Hydrochloride, Docetaxel, and contrast agents and achieved a significantly higher concomitant accumulation in tumor versus free drugs, demonstrating that nanoparticles can improve synergistic cancer chemotherapy

Organosilicon phantom for photoacoustic imaging

Photoacoustic imaging is an emerging technique. Although commercially available photoacoustic imaging systems currently exist, the technology is still in its infancy. Therefore, the design of stable phantoms is essential to achieve semiquantitative evaluation of the performance of a photoacoustic system and can help optimize the properties of contrast agents. We designed and developed a polydimethylsiloxane (PDMS) phantom with exceptionally fine geometry; the phantom was tested using photoacoustic experiments loaded with the standard indocyanine green dye and compared to an agar phantom pattern through polyethylene glycol-gold nanorods. The linearity of the photoacoustic signal with the nanoparticle number was assessed. The signal-to-noise ratio and contrast were employed as image quality parameters, and enhancements of up to 50 and up to 300%, respectively, were measured with the PDMS phantom with respect to the agar one. A tissue-mimicking (TM)-PDMS was prepared by adding TiO2 and India ink; photoacoustic tests were performed in order to compare the signal generated by the TM-PDMS and the biological tissue. The PDMS phantom can become a particularly promising tool in the field of photoacoustics for the evaluation of the performance of a PA system and as a model of the structure of vascularized soft tissues. (C) 2015 Society of Photo-Optical Instrumentation Engineers (SPIE

Using ice core measurements from Taylor Glacier, Antarctica, to calibrate in situ cosmogenic 14 C production rates by muons

Cosmic rays entering the Earth’s atmosphere produce showers of secondary particles such as protons, neutrons, and muons. The interaction of these particles with oxygen-16 (16O) in minerals such as ice and quartz can produce carbon-14 (14C). In glacial ice, 14C is also incorporated through trapping of 14C-containing atmospheric gases (14CO2, 14CO, and 14CH4). Understanding the production rates of in situ cosmogenic 14C is important to deconvolve the in situ cosmogenic and atmospheric 14C signals in ice, both of which contain valuable paleoenvironmental information. Unfortunately, the in situ 14C production rates by muons (which are the dominant production mechanism at depths of > 6m solid ice equivalent) are uncertain. In this study, we use measurements of in situ 14C in ancient ice (> 50 ka) from the Taylor Glacier, an ablation site in Antarctica, in combination with a 2D ice flow model to better constrain the compound-specific rates of 14C production by muons and the partitioning of in situ 14C between CO2, CO, and CH4. Our measurements show that 33.7% (11.4%; 95% confidence interval) of the produced cosmogenic 14C forms 14CO and 66.1% (11.5%; 95% confidence interval) of the produced cosmogenic 14C forms 14CO2. 14CH4 represents a very small fraction (< 0.3%) of the total. Assuming that the majority of in situ muogenic 14C in ice forms 14CO2, 14CO, and 14CH4, we also calculated muogenic 14C production rates that are lower by factors of 5.7 (3.6–13.9; 95% confidence interval) and 3.7 (2.0–11.9; 95% confidence interval) for negative muon capture and fast muon interactions, respectively, when compared to values determined in quartz from laboratory studies (Heisinger et al., 2002a, b) and in a natural setting (Lupker et al., 2015). This apparent discrepancy in muogenic 14C production rates in ice and quartz currently lacks a good explanation and requires further investigation

Costruzione, implementazione e validazione di phantoms per lo studio in vitro di materiali nanostrutturati nell'imaging fotoacustico

• Background Il fenomeno fotoacustico consiste nella generazione di onde acustiche all'interno di un materiale per mezzo di fenomeni di termoespansione, che sono indotti da una stimolazione laser cadenzata. L'utilizzo della fotoacustica nell'ambito delle tecnologie mediche sta prendendo sempre più campo, grazie al binomio della capacità penetrativa delle onde acustiche con l'alta risoluzione derivata dallo scattering ottico all'interno dei tessuti. La fotoacustica è ancora una tecnica giovane perciò non sono stati ancora creati alcun tipo di protocolli di misura oppure di phantoms mirati alle differenti tipologie di indagine, che il metodo permette. • Scopo Il lavoro di questa tesi si colloca nella problematica di progettazione, implementazione e validazione di phantoms adatti allo studio di potenziali agenti di contrasto per applicazioni fotoacustiche. • Materiali e metodi Sono stati scelti due materiali (agar e polidimetilsilossano) e sviluppati con essi tre tipologie di phantoms, di cui uno con proprietà tessuto equivalente. Questi phantoms sono stati studiati, caratterizzandone il comportamento fotoacustico, per mezzo sia di coloranti quali il blu di metilene e l'indocianina verde che di nanoparticelle di caratteristiche note. Le misure sono state effettuate tramite la piattaforma fotoacustica Vevo LAZR (FUJIFILM VisualSonics Inc. , Toronto, ON, Canada). • Conclusioni Alla luce dei risultati, la scelta dei materiali e le relative modalità di uso e costruzione si sono rivelate efficaci sia in termini di basso segnale di background che in termini di parametri qualitativi di imaging come SNR e contrasto con gli agenti utilizzati. In conclusione, con questo lavoro di tesi sono stati progettati, realizzati e testati phantoms per applicazioni fotoacustiche, che possono essere utilizzati per standardizzare e rendere riproducibili le procedure di valutazione di nuovi agenti di contrasto

Effects of mineral weathering and acid mine drainage on Pco2 in Davis Mine Brook and Maxwell Brook Watersheds, Rowe, Ma.

Acid mine drainage (AMD), an acidic iron-rich leachate that is characterized by low pH and high concentrations of sulfate and dissolved metals, is the most important mining-related water pollution problem in the world. AMD has the potential to affect the global carbon cycle by releasing CO2 to the atmosphere because the high acidity converts dissolved inorganic carbon species to CO2 gas, increasing the PCO2 of the water. Often, investigators studying PCO2 generation associated with AMD have focused on regions where acid mine waters interact with carbonate rocks because carbonate minerals chemically weather quickly and have the potential to generate significant CO2(g) if pH remains low. In contrast, this study focuses on PCO2 production related to AMD in a silicate rock setting at the historic Davis Pyrite Mine, which is situated in the Hawley-Rowe metamorphic rock belt in Rowe, Massachusetts. For the past century, pyrite rich tailings have been left in the riparian zone of Davis Mine Brook, exposed to weathering as groundwater flows through them and into the stream. Adjacent to the Davis Mine Brook watershed is the Maxwell Brook watershed. While both streams are underlain by the same bedrock, there is no apparent influence of the mining activities on the Maxwell Brook watershed, which serves as a neutral water reference for the acidic conditions of Davis Mine Brook. Comparing these two watersheds provides insight on how mineral weathering in different levels of acidity may contribute to the water chemistry observed in each setting. Water and rock samples from Davis Mine Brook and Maxwell Brook watersheds were collected in August and November, 2017. Surface water samples were collected in both watersheds, and seep and drainage samples were collected from tailings piles along Davis Mine Brook. Thin sections were analyzed with petrographic light and scanning electron microscopy. Water samples were analyzed directly for carbon, dissolved major ion, silica, iron, and aluminum concentrations, as well as d18O and d2H isotopes. Special focus is given to PCO2 concentrations, and an in-depth exploration of methodology for calculating PCO2 from field data and inorganic carbon analyses is outlined. Differences in water chemistry and PCO2 concentrations in Davis Mine Brook surface and seep water samples compared to the references samples are traced back to mineral weathering reactions based on rock sample observations. PCO2 is supersaturated in all samples relative to the atmospheric level, but the seep and drainage samples are extremely elevated, by up to six orders of magnitude (logPCO2atm = -3.4; mean reference surface waters = logPCO2 = -0.9; mean DMB surface waters = logPCO2 = 1.1; mean DMB groundwater seeps and mine drainage waters = logPCO2 = 3). Graphite is identified as a mineral source for the elevated PCO2 in acidic mine water. Lower PCO2 in Davis Mine Brook stream water located downstream of the mine appears to result from a combination of degassing and conversion of CO2(g) to carbonic acid and bicarbonate ion. These results suggest that minor amounts of graphite in metamorphic rocks weathered by AMD can cause a noteworthy CO2 flux to the atmosphere