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Nanoscience breakthroughs in almost every field of science and nanotechnologies make life easier in this era. Nanoscience and nanotechnology represent an expanding research area, which involves structures, devices, and systems with novel properties and functions due to the arrangement of their atoms on the 1-100 nm scale. The field was subject to a growing public awareness and controversy in the early 2000s, and in turn, the beginnings of commercial applications of nanotechnology. Nanotechnologies contribute to almost every field of science, including physics, materials science, chemistry, biology, computer science, and engineering. Notably, in recent years nanotechnologies have been applied to human health with promising results, especially in the field of cancer treatment. To understand the nature of nanotechnology, it is helpful to review the timeline of discoveries that brought us to the current understanding of this science. This review illustrates the progress and main principles of nanoscience and nanotechnology and represents the pre-modern as well as modern timeline era of discoveries and milestones in these fields.

Computer-aided drug design techniques are today largely applied in medicinal chemistry. In particular, receptor-based virtual screening (VS) studies, in which molecular docking represents the gold standard in silico approach, constitute a powerful strategy for identifying novel hit compounds active against the desired target receptor. Nevertheless, the need for improving the ability of docking in discriminating true active ligands from inactive compounds, thus boosting VS hit rates, is still pressing. In this context, the use of binding free energy evaluation approaches can represent a profitable tool for rescoring ligand-protein complexes predicted by docking based on more reliable estimations of ligand-protein binding affinities than those obtained with simple scoring functions. In the present review, we focused our attention on the Molecular Mechanics-Poisson Boltzman Surface Area (MM-PBSA) method for the calculation of binding free energies and its application in VS studies. We provided examples of successful applications of this method in VS campaigns and evaluation studies in which the reliability of this approach has been assessed, thus providing useful guidelines for employing this approach in VS.

PD-L1 (programmed cell death ligand-1) is a protein located on the surface of regulatory cells. It has an immunosuppressive role as it binds specifically to the protein programmed cell death-1 (PD-1), a checkpoint glycoprotein, present on the surface of immune cells such as T and B lymphocytes. Many tumor cells block the immune response by overexpressing PD-L1 on their surface; therefore, targeting PD-L1 represents a powerful strategy that allows tumor localization. To determine the presence of PD-L1 in cells, the use of ad hoc functionalized peptides that bind to PD-L1 can be exploited. One of them is the peptide CLP002 (Trp-His-Arg-Ser-Tyr-Tyr-Thr-Trp-Asn-Leu-Asn-Thr), which, bound to surface-enhanced Raman scattering (SERS) gold nanostructures via a suitable linker, was shown to be highly effective in recognizing MDA-MB-231 breast cancer cells and, importantly, this recognition can be measured by SERS experiments. To characterize, on a molecular scale, the interaction between PD-L1 and peptide functionalized nanostructures, we performed molecular dynamics (MDs) simulations, studying the features of peptide monolayers bound on gold surfaces in the absence and presence of PD-L1. The results obtained allow us to explain why the nature of the linker plays a fundamental role in the binding and why a peptide carrying the same amino acids as CPL002 but with a different sequence (scrambled) is much less active than CLP002. These results open the way to an in silico evaluation of the key parameters that regulate the binding of PD-L1 useful for cancer recognition.

To test the efficacy and toxicity of exosomal doxorubicin (exoDOX) compared with free doxorubicin. The cytotoxic effects of exoDOX were tested and in nude mice by measuring the tumor volume. The toxic effects were evaluated by measuring the bodyweight and through histopathologic analyses. The biodistribution of DOX was assessed by MS. and studies showed that exosomes did not decrease the efficacy of DOX. Surprisingly, exoDOX showed no cardiotoxicity as observed in DOX-treated mice and MS studies confirmed that the accumulation of exoDOX in the heart was reduced by approximately 40%. We demonstrated that exoDOX was less toxic than DOX through its altered biodistribution.

Amiodarone repositioning in cancer treatment is promising, however toxicity limits seem to arise, constraining its exploitability. Notably, amiodarone has been investigated for the treatment of ovarian cancer, a tumour known for metastasizing within the peritoneal cavity. This is associated with an increase of fatty acid oxidation, which strongly depends on CPT1A, a transport protein which has been found overexpressed in ovarian cancer. Amiodarone is an inhibitor of CPT1A but its role still has to be explored. Therefore, in the present study, amiodarone was tested on ovarian cancer cell lines with a focus on lipid alteration, confirming its activity. Moreover, considering that drug delivery systems could lower drug side effects, microfluidics was employed for the development of drug delivery systems of amiodarone obtaining simultaneously liposomes with a high payload and amiodarone particles. Prior to amiodarone loading, microfluidics production was optimized in term of temperature and flow rate ratio. Moreover, stability over time of particles was evaluated. In vitro tests confirmed the efficacy of the drug delivery systems.

A wide range of platinum(0)-η2-(E)-1,2-ditosylethene complexes bearing isocyanide, phosphine and N-heterocyclic carbene ancillary ligands have been prepared with high yields and selectivity. All the novel products underwent thorough characterization using spectroscopic techniques, including NMR and FT-IR analyses. Additionally, for some compounds, the solid-state structures were elucidated through X-ray diffractometry. The synthesized complexes were successively evaluated for their potential as anticancer agents against two ovarian cancer cell lines (A2780 and A2780cis) and one breast cancer cell line (MDA-MB-231). The majority of the compounds displayed promising cytotoxicity within the micromolar range against A2780 and MDA-MB-231 cells, with IC50 values comparable to or even surpassing those of cisplatin. However, only a subset of compounds was cytotoxic against cisplatin-resistant cancer cells (A2780cis). Furthermore, the assessment of antiproliferative activity on MRC-5 normal cells revealed certain compounds to exhibit in vitro selectivity. Notably, complexes 3d, 6a and 6b showed low cytotoxicity towards normal cells (IC50 > 100 µM) while concurrently displaying potent cytotoxicity against cancer cells.

Cisplatin (CDDP) is commonly used to treat a multitude of tumors including sarcomas, ovarian and cervical cancers. Despite recent investigations allowed to improve chemotherapy effectiveness, the molecular mechanisms underlying the development of CDDP resistance remain a major goal in cancer research. Here, we show that mitochondrial morphology and autophagy are altered in different CDDP resistant cancer cell lines. In CDDP resistant osteosarcoma and ovarian carcinoma, mitochondria are fragmented and closely juxtaposed to the endoplasmic reticulum; rates of mitophagy are also increased. Specifically, levels of the mitophagy receptor BNIP3 are higher both in resistant cells and in ovarian cancer patient samples resistant to platinum-based treatments. Genetic BNIP3 silencing or pharmacological inhibition of autophagosome formation re-sensitizes these cells to CDDP. Our study identifies inhibition of BNIP3-driven mitophagy as a potential therapeutic strategy to counteract CDDP resistance in ovarian carcinoma and osteosarcoma. BNIP3-mediated mitochondrial clearance as a mechanism underlying resistance to cisplatin CDDP induces the stabilization of HIF-1α that leads to the expression of its target gene BNIP3. BNIP3 promotes autophagy of mitochondria by increasing their fission and degradation rates. This process ultimately boosts the ability of resistant cancer cells to escape CDDP cytotoxicity by eliminating one of its main targets, mitochondria, from which cytochrome c is released to initiate cell death. While BNIP3 expression could be a new prognostic factor to predict the chemotherapy responsiveness of cancer patients, targeting mitophagy could be a new therapeutic approach to overcome platinum resistance. We used BioRender Software (BioRender.com) to draw the schematic picture.

The synthesis of Co-based two-dimensional (2D) metal azolate framework nanosheets (MAF-5-Co II NS) is described using a simple hydrothermal method. The product was isostructural to MAF-5 (Zn). The as-prepared MAF-5-Co II NS exhibited high surface area (1155 m 2 /g), purity, and crystallinity. The MAF-5-Co II NS–modified screen-printed electrode (MAF-5-Co II NS/SPE) was used for nonenzymatic detection of glucose in diluted human blood plasma (BP) samples with phosphate buffer saline (PBS, pH 7.4) and NaOH (0.1 M, pH 13.0) solutions. The MAF-5-Co II NS nanozyme displayed good redox activity in both neutral and alkaline media with the formation of Co II /Co III redox pair, which induced the catalytic oxidation of glucose. Under the optimized detection potential, the sensor presented a chronoamperometric current response for the oxidation of glucose with two wide concentration ranges in PBS-diluted (62.80 to 180 μM and 305 to 8055 μM) and NaOH-diluted (58.90 to 117.6 μM and 180 to 10,055 μM) BP samples, which were within the limit of blood glucose levels of diabetic patients before (4.4–7.2 mM) and after (10 mM) meals (recommended by the American Diabetes Association). The sensor has a limit of detection of ca. 0.25 and 0.05 μM, respectively, and maximum sensitivity of ca. 36.55 and 1361.65 mA/cm 2 /mM, respectively, in PBS- and NaOH-diluted BP samples. The sensor also displayed excellent stability in the neutral and alkaline media due to the existence of hydrophobic linkers (2-ethyl imidazole) in the MAF-5-Co II NS, good repeatability and reproducibility, and interference-free signals. Thus, MAF-5-Co II NS is a promising nanozyme for the development of the disposable type of sensor for glucose detection in human body fluids. Graphical abstract

In this work, MnZn ferrite nanoparticles with hierarchical morphology were synthesized hydrothermally, and their surface characteristics were improved by the PEGylation process. In vitro MRI studies were also conducted to evaluate the ability of the synthesized nanoparticles as a contrast agent. All results were compared with those obtained for MnZn ferrite nanoparticles with normal structure. Microstructural evaluations showed that in ferrite with hierarchical morphology, the spherical particles with an average size of ~20 nm made a distinctive structure consisting of rows of nanoparticles which is a relatively big assembly like a dandelion. The smaller particle size and dandelion-like morphology led to an increase in specific surface area for the hierarchical structure (~69 m2/g) in comparison to the normal one (~30 m2/g) with an average particle size of ~40 nm. In vitro MRI, cytotoxicity and hemocompatibility assays confirmed the PEG-coated MnZn ferrite nanoparticles with hierarchical structure synthesized in the current study can be considered as an MRI contrast agent.

A new class of palladium–indenyl complexes characterized by the presence of one bulky alkyl isocyanide and one aryl phosphine serving as ancillary ligands has been prepared, presenting high yields and selectivity. All the new products were completely characterized using spectroscopic and spectrometric techniques (NMR, FT-IR, and HRMS), and, for most of them, it was also possible to define their solid-state structures via X-ray diffractometry, revealing that the indenyl fragment always binds to the metal centre with a hapticity intermediate between ƞ3 and ƞ5. A reactivity study carried out using piperidine as a nucleophilic agent proved that the indenyl moiety is the eligible site of attack rather than the isocyanide ligand or the metal centre. All complexes were tested as potential anticancer agents against three ovarian cancer cell lines (A2780, A2780cis, and OVCAR-5) and one breast cancer cell line (MDA-MB-231), displaying comparable activity with respect to cisplatin, which was used as a positive control. Moreover, the similar cytotoxicity observed towards A2780 and A2780cis cells (cisplatin-sensitive and cisplatin-resistant, respectively) suggests that our palladium derivatives presumably act with a mechanism of action different than that of the clinically approved platinum drugs. For comparison, we also synthesized Pd-ƞ3-allyl derivatives, which generally showed a slightly higher activity towards ovarian cancer cells and lower activity towards breast cancer cells with respect to their Pd-indenyl congeners.