Luminescent Alendronic Acid-Conjugated Micellar Nanostructures for Potential Application in the Bone-Targeted Delivery of Cholecalciferol.

Vitamin D, an essential micronutrient crucial for skeletal integrity and various non-skeletal physiological functions, exhibits limited bioavailability and stability in vivo. This study is focused on the development of polyethylene glycol (PEG)-grafted phospholipid micellar nanostructures co-encapsulating vitamin D3 and conjugated with alendronic acid, aimed at active bone targeting. Furthermore, these nanostructures are rendered optically traceable in the UV-visible region of the electromagnetic spectrum via the simultaneous encapsulation of vitamin D3 with carbon dots, a newly emerging class of fluorescents, biocompatible nanoparticles characterized by their resistance to photobleaching and environmental friendliness, which hold promise for future in vitro bioimaging studies. A systematic investigation is conducted to optimize experimental parameters for the preparation of micellar nanostructures with an average hydrodynamic diameter below 200 nm, ensuring colloidal stability in physiological media while preserving the optical luminescent properties of the encapsulated carbon dots. Comprehensive chemical-physical characterization of these micellar nanostructures is performed employing optical and morphological techniques. Furthermore, their binding affinity for the principal inorganic constituent of bone tissue is assessed through a binding assay with hydroxyapatite nanoparticles, indicating significant potential for active bone-targeting. These formulated nanostructures hold promise for novel therapeutic interventions to address skeletal-related complications in cancer affected patients in the future.

Au nanoparticles decorated nanographene oxide-based platform: Synthesis, functionalization and assessment of photothermal activity.

A novel hybrid nanocomposite formed of carboxylated Nano Graphene Oxide (c-NGO), highly densely decorated by monodisperse citrate-coated Au nanoparticles (c-NGO/Au NPs), is synthesized and thoroughly characterized for photothermal applications. A systematic investigation of the role played by the synthetic parameters on the Au NPs decoration of the c-NGO platform is performed, comprehensively studying spectroscopic and morphological characteristics of the achieved nanostructures, thus elucidating their still not univocally explained synthesis mechanism. Remarkably, the Au NPs coating density of the c-NGO sheets is much higher than state-of-the-art systems with analogous composition prepared with different approaches, along with a higher NPs size dispersion. A novel theoretical approach for estimating the average number of NPs per sheet, combining DLS and TEM results, is developed. The assessment of the c-NGO/Au NPs photothermal activity is performed under continuous wave (CW) laser irradiation, at 532 nm and 800 nm, before and after functionalization with PEG-SH. c-NGO/Au NPs composite behaves as efficient photothermal agent, with a light into heat conversion ability higher than that of the single components. The c-NGO/Au NPs compatibility for photothermal therapy is assessed by in vitro cell viability tests, which show no significant effects of c-NGO/Au NPs, as neat and PEGylated, on cell metabolic activity under the investigated conditions. These results demonstrate the great potential held by the prepared hybrid nanocomposite for photothermal conversion technologies, indicating it as particularly promising platform for photothermal ablation of cancer cells.

NIR-Absorbing Mesoporous Silica-Coated Copper Sulphide Nanostructures for Light-to-Thermal Energy Conversion.

Plasmonic nanostructures, featuring near infrared (NIR)-absorption, are rising as efficient nanosystems for in vitro photothermal (PT) studies and in vivo PT treatment of cancer diseases. Among the different materials, new plasmonic nanostructures based on Cu2-xS nanocrystals (NCs) are emerging as valuable alternatives to Au nanorods, nanostars and nanoshells, largely exploited as NIR absorbing nanoheaters. Even though Cu2-xS plasmonic properties are not linked to geometry, the role played by their size, shape and surface chemistry is expected to be fundamental for an efficient PT process. Here, Cu2-xS NCs coated with a hydrophilic mesoporous silica shell (MSS) are synthesized by solution-phase strategies, tuning the core geometry, MSS thickness and texture. Besides their loading capability, the silica shell has been widely reported to provide a more robust plasmonic core protection than organic molecular/polymeric coatings, and improved heat flow from the NC to the environment due to a reduced interfacial thermal resistance and direct electron-phonon coupling through the interface. Systematic structural and morphological analysis of the core-shell nanoparticles and an in-depth thermoplasmonic characterization by using a pump beam 808 nm laser, are carried out. The results suggest that large triangular nanoplates (NPLs) coated by a few tens of nanometers thick MSS, show good photostability under laser light irradiation and provide a temperature increase above 38 °C and a 20% PT efficiency upon short irradiation time (60 s) at 6 W/cm2 power density.

Plasma Treated Water Solutions in Cancer Treatments: The Contrasting Role of RNS.

Plasma Treated Water Solutions (PTWS) recently emerged as a novel tool for the generation of Reactive Oxygen and Nitrogen Species (ROS and RNS) in liquids. The presence of ROS with a strong oxidative power, like hydrogen peroxide (H2O2), has been proposed as the main effector for the cancer-killing properties of PTWS. A protective role has been postulated for RNS, with nitric oxide (NO) being involved in the activation of antioxidant responses and cell survival. However, recent evidences proved that NO-derivatives in proper mixtures with ROS in PTWS could enhance rather than reduce the selectivity of PTWS-induced cancer cell death through the inhibition of specific antioxidant cancer defenses. In this paper we discuss the formation of RNS in different liquids with a Dielectric Barrier Discharge (DBD), to show that NO is absent in PTWS of complex composition like plasma treated (PT)-cell culture media used for in vitro experiments, as well as its supposed protective role. Nitrite anions (NO2-) instead, present in our PTWS, were found to improve the selective death of Saos2 cancer cells compared to EA.hy926 cells by decreasing the cytotoxic threshold of H2O2 to non-toxic values for the endothelial cell line.

Oil-Dispersible Green-Emitting Carbon Dots: New Insights on a Facile and Efficient Synthesis.

Carbon dots (CDs) have been progressively attracting interest as novel environmentally friendly and cost-effective luminescent nanoparticles, for implementation in light-emitting devices, solar cells, photocatalytic devices and biosensors. Here, starting from a cost-effective bottom-up synthetic approach, based on a suitable amphiphilic molecule as carbon precursor, namely cetylpyridinium chloride (CPC), green-emitting CDs have been prepared at room temperature, upon treatment of CPC with concentrated NaOH solutions. The investigated method allows the obtaining, in one-pot, of both water-dispersible (W-CDs) and oil-dispersible green-emitting CDs (O-CDs). The study provides original insights into the chemical reactions involved in the process of the carbonization of CPC, proposing a reliable mechanism for the formation of the O-CDs in an aqueous system. The ability to discriminate the contribution of different species, including molecular fluorophores, allows one to properly single out the O-CDs emission. In addition, a mild heating of the reaction mixture, at 70 °C, has demonstrated the ability to dramatically decrease the very long reaction time (i.e. from tens of hours to days) at room temperature, allowing us to synthesize O-CDs in a few tens of minutes while preserving their morphological and optical properties.

Gold-Speckled SPION@SiO2 Nanoparticles Decorated with Thiocarbohydrates for ASGPR1 Targeting: Towards HCC Dual Mode Imaging Potential Applications.

Efforts are made to perform an early and accurate detection of hepatocellular carcinoma (HCC) by simultaneous exploiting multiple clinically non-invasive imaging modalities. Original nanostructures derived from the combination of different inorganic domains can be used as efficient contrast agents in multimodal imaging. Superparamagnetic iron oxide nanoparticles (SPIONs) and Au nanoparticles (NPs) possess well-established contrasting features in magnetic resonance imaging (MRI) and X-ray computed tomography (CT), respectively. HCC can be targeted by using specific carbohydrates able to recognize asialoglycoprotein receptor 1 (ASGPR1) overexpressed in hepatocytes. Here, two different thiocarbohydrate ligands were purposely designed and alternatively conjugated to the surface of Au-speckled silica-coated SPIONs NPs, to achieve two original nanostructures that could be potentially used for dual mode targeted imaging of HCC. The results indicated that the two thiocarbohydrate decorated nanostructures possess convenient plasmonic/superparamagnetic properties, well-controlled size and morphology and good selectivity for targeting ASGPR1 receptor.

FZD10 Carried by Exosomes Sustains Cancer Cell Proliferation.

Extracellular vesicles (EVs) are involved in intercellular communication during carcinogenesis, and cancer cells are able to secrete EVs, in particular exosomes containing molecules, that can be transferred to recipient cells to induce pathological processes and significant modifications, as metastasis, increase of proliferation, and carcinogenesis evolution. FZD proteins, a family of receptors comprised in the Wnt signaling pathway, play an important role in carcinogenesis of the gastroenteric tract. Here, a still unknown role of Frizzled 10 (FZD10) protein was identified. In particular, the presence of FZD10 and FZD10-mRNA in exosomes extracted from culture medium of the untreated colorectal, gastric, hepatic, and cholangio cancer cell lines, was detected. A substantial reduction in the FZD10 and FZD10-mRNA level was achieved in FZD10-mRNA silenced cells and in their corresponding exosomes. Concomitantly, a significant decrease in viability of the silenced cells compared to their respective controls was observed. Notably, the incubation of silenced cells with the exosomes extracted from culture medium of the same untreated cells promoted the restoration of the cell viability and, also, of the FZD10 and FZD10-mRNA level, thus indicating that the FZD10 and FZD10-mRNA delivering exosomes may be potential messengers of cancer reactivation and play an active role in long-distance metastatization.

Green Fluorescent Terbium (III) Complex Doped Silica Nanoparticles.

The low photostability of conventional organic dyes and the toxicity of cadmium-based luminescent quantum dots have prompted the development of novel probes for in vitro and in vivo labelling. Here, a new fluorescent lanthanide probe based on silica nanoparticles is fabricated and investigated for optically traceable in vitro translocator protein (TSPO) targeting. The targeting and detection of TSPO receptor, overexpressed in several pathological states, including neurodegenerative diseases and cancers, may provide valuable information for the early diagnosis and therapy of human disorders. Green fluorescent terbium(III)-calix[4]arene derivative complexes are encapsulated within silica nanoparticles and surface functionalized amine groups are conjugated with selective TSPO ligands based on a 2-phenylimidazo[1,2-a]pyridine acetamide structure containing derivatizable carboxylic groups. The photophysical properties of the terbium complex, promising for biological labelling, are demonstrated to be successfully conveyed to the realized nanoarchitectures. In addition, the high degree of biocompatibility, assessed by cell viability assay and the selectivity towards TSPO mitochondrial membrane receptors, proven by subcellular fractional studies, highlight targeting potential of this nanostructure for in vitro labelling of mitochondria.

Imaging modification of colon carcinoma cells exposed to lipid based nanovectors for drug delivery: a scanning electron microscopy investigation.

The adsorption at cell surfaces and cell internalization of two drug delivery lipid based nanovectors has been investigated by means of Field Emission Scanning Electron Microscopy (FE-SEM) operating at low beam voltage on two different colon carcinoma cell lines, CaCo-2 and CoLo-205, that were compared with the M14 melanoma cell line, as a reference. The cells were incubated with the investigated multifunctional nanovectors, based on liposomes and magnetic micelles loaded with 5-fluorouracil, as a chemotherapeutic agent, and a FE-SEM systematic investigation was performed, enabling a detailed imaging of any morphological changes of the drug exposed cells as a function of time. The results of the FE-SEM investigation were validated by MTS assay and immunofluorescence staining of the Ki-67 protein performed on the investigated cell lines at different times. The two nanoformulations resulted in a comparable effect on CaCo-2 and M14 cell lines, while for CoLo 205 cells, the liposomes provided an cytotoxic activity higher than that observed in the case of the micelles. The study highlighted the high potential of FE-SEM as a valuable complementary technique for imaging and monitoring in time the drug effects on the selected cells exposed to the two different nanoformulations.