Nanoheterostructures (NHS) and Their Applications in Nanomedicine: Focusing on In Vivo Studies

Inorganic nanoparticles have great potential for application in many fields, including nanomedicine. Within this class of materials, inorganic nanoheterostructures (NHS) look particularly promising as they can be formulated as the combination of different domains; this can lead to nanosystems with different functional properties, which, therefore, can perform different functions at the same time. This review reports on the latest development in the synthesis of advanced NHS for biomedicine and on the tests of their functional properties in in vivo studies. The literature discussed here focuses on the diagnostic and therapeutic applications with special emphasis on cancer. Considering the diagnostics, a description of the NHS for cancer imaging and multimodal imaging is reported; more specifically, NHS for magnetic resonance, computed tomography and luminescence imaging are considered. As for the therapeutics, NHS employed in magnetic hyperthermia or photothermal therapies are reported. Examples of NHS for cancer theranostics are also presented, emphasizing their dual usability in vivo, as imaging and therapeutic tools. Overall, NHS show a great potential for biomedicine application; further studies, however, are necessary regarding the safety associated to their use

Acute Cytotoxic Effects on Morphology and Mechanical Behavior in MCF-7 Induced by TiO2NPs Exposure

The side effects induced by nanoparticle exposure at a cellular level are one of the priority research topics due to the steady increase in the use of nanoparticles (NPs). Recently, the focus on cellular morphology and mechanical behavior is gaining relevance in order to fully understand the cytotoxic mechanisms. In this regard, we have evaluated the morphomechanical alteration in human breast adenocarcinoma cell line (MCF-7) exposed to TiO2NPs at two different concentrations (25 and 50 µg/mL) and two time points (24 and 48 h). By using confocal and atomic force microscopy, we demonstrated that TiO2NP exposure induces significant alterations in cellular membrane elasticity, due to actin proteins rearrangement in cytoskeleton, as calculated in correspondence to nuclear and cytoplasmic compartments. In this work, we have emphasized the alteration in mechanical properties of the cellular membrane, induced by nanoparticle exposure

Pencil Graphite Electrocatalytic Sensors Modified by Pyrene Coated Reduced Graphene Oxide Decorated with Molybdenum Disulfide Nanoroses for Hydrazine and 4-Nitrophenol Detection in Real Water Samples

Novel nanostructured platforms based on Pencil Graphite Electrodes (PGEs), modified with pyrene carboxylic acid (PCA) functionalized Reduced Graphene Oxide (rGO), and then decorated by chronoamperometry electrodeposition of MoS2 nanoroses (NRs) (MoS(2)NRs/PCA-rGO/PGEs) were manufactured for the electrocatalytic detection of hydrazine (N2H4) and 4-nitrophenol, pollutants highly hazardous for environment and human health. The surface morphology and chemistry of the MoS(2)NRs/PCA-rGO/PGEs were characterized by scanning electron microscopy (SEM), Raman, and X-ray photoelectron spectroscopy (XPS), assessing the coating of the PCA-rGO/PGEs by dense multilayers of NRs. N2H4 and 4-nitrophenol have been monitored by Differential Pulse Voltammetry (DPV), and the MoS(2)NRs/PCA-rGO/PGEs electroanalytical properties have been compared to the PGEs, as neat and modified by PCA-rGO. The MoS(2)NRs/PCA-rGO/PGEs demonstrated a higher electrochemical and electrocatalytic activity, due to their high surface area and conductivity, and very fast heterogeneous electron transfer kinetics at the interphase with the electrolyte. LODs lower than the U.S. EPA recommended concentration values in drinking water, namely 9.3 nM and 13.3 nM, were estimated for N2H4 and 4-nitrophenol, respectively and the MoS(2)NRs/PCA-rGO/PGEs showed good repeatability, reproducibility, storage stability, and selectivity. The effectiveness of the nanoplatforms for monitoring N2H4 and 4-nitrophenol in tap, river, and wastewater was addressed

Electrochemical Sensors Based on Au Nanoparticles Decorated Pyrene-Reduced Graphene Oxide for Hydrazine, 4-Nitrophenol and Hg2+ Detection in Water

Monitoring hazardous chemical compounds such as hydrazine (N2H4), 4-nitrophenol (4-NP) and Hg2+ in natural water resources is a crucial issue due to their toxic effects on human health and catastrophic impact on the environment. Electrochemical nanostructured platforms integrating hybrid nanocomposites based on graphene derivatives and inorganic nanoparticles (NPs) are of great interest for such a purpose. In this work, disposable screen-printed carbon electrodes (SPCEs) have been modified with a hybrid nanocomposite formed by reduced graphene oxide (RGO), functionalized by 1-pyrene carboxylic acid (PCA), and decorated by colloidal Au NPs. These hybrid platforms have been tested for the electrocatalytic detection of N2H4 and 4-NP by differential pulse voltammetry and have been modified with an electropolymerized film of Hg2+ ions imprinted polycurcumin for the electroanalytical detection of Hg2+ by DPV. LODs, lower and in line with the lowest ones reported for state-of-the-art electrochemical sensors, integrating similar Au-graphene < nanocomposites, have been estimated. Additionally, good repeatability, reproducibility, and storage stability have been assessed, as well as a high selectivity in the presence of a 100-fold higher concentration of interfering species. The applicability of the proposed platforms for the detection of the compounds in real complex matrices, such as tap and river water samples, has been effectively demonstrated

Design and Application of Cisplatin-Loaded Magnetic Nanoparticle Clusters for Smart Chemotherapy

One of the major challenges of drug delivery is the development of suitable carriers for therapeutic molecules. In this work, a novel nanoformulation based on superparamagnetic nanoclusters [magnetic nanocrystal clusters (MNCs)] is presented. In order to control the size of the nanoclusters and the density of magnetic cores, several parameters were evaluated and tuned. Then, MNCs were functionalized with a polydopamine layer (MNC@PDO) to improve their stability in aqueous solution, to increase density of functional groups and to obtain a nanosystem suitable for drug-controlled release. Finally, cisplatin was grafted on the surface of MNC@PDO to exploit the system as a magnetic field-guided anticancer delivery system. The biocompatibility of MNC@PDO and the cytotoxic effects of MNC@PDO–cisplatin complex were determined against human cervical cancer (HeLa) and human breast adenocarcinoma (MCF-7) cells. In vitro studies demonstrated that the MNC@PDO–cisplatin complexes inhibited the cellular proliferation by a dose-dependent effect. Therefore, by applying an external magnetic field, the released drug exerted its effect on a specific target area. In summary, the MNC@PDO nanosystem has a great potential to be used in targeted nanomedicine for the delivery of other drugs or biofunctional molecules

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

Tumor Cell Transendothelial Passage in the Absorbing Lymphatic Vessel of Transgenic Adenocarcinoma Mouse Prostate

The distribution and fine structure of the tumor-associated absorbing lymphatic vessel in the tumor mass of prostate adenocarcinoma and of seminal vesicle metastasis in transgenic mice was studied for the purpose of understanding the modality of tumor cell transendothelial passage from the extravasal matrix into the lymphatic vessel. In the tumor mass, two main cell populations were identified: stromal tumor cells and the invasive phenotype tumor (IPT) cells, having characteristics such as a highly electron-dense matrix rich in small granules lacking a dense core and massed nuclear chromatin, which is positive to immunostaining with anti-SV40 large T antigen antibody. Based on the ultrastructural pictures of different moments of the IPT cell transendothelial passage by ultrathin serial sections of the tumor-associated absorbing lymphatic vessel, the manner of its transendothelial passage through the intraendothelial channel, without involving intercellular contacts, was demonstrated. The presence of IPT cells in the parenchyma of satellite lymph node highlights its significant role in metastatic diffusion. The intraendothelial channel is the reply to the lack of knowledge regarding the intravasation of the tumor cell into the lymphatic circulation. The lymphatic endothelium would organize this channel on the basis of tumor cell-endothelial cell-extravasal matrix molecular interactions, which are as yet unidentified