The novel [Pt(O,O′-acac)(γ-acac)(DMS)], Ptac2S, Pt(II) complex has recently gained increasing attention as a potential anticancer agent for its pharmacological activity shown in different tumor cell lines, studied both in vitro and in vivo. The mechanism of action of Ptac2S, operating on non-genomic targets, is known to be very different from that of cis-[PtCl2(NH3)2], cisplatin, targeting nucleic acids. In this work, we evaluated the cytotoxicity of Ptac2S on the cisplatin resistant Epithelial Ovarian Carcinoma (EOC), SKOV-3 cells, by the MTT assay. A 1H-NMR metabolomic approach coupled with multivariate statistical analysis was used for the first time for Ptac2S to figure out the biological mechanisms of action of the complex. The metabolic variations of intracellular metabolites and the composition of the corresponding extracellular culture media were compared to those of cisplatin (cells were treated at the IC50 doses of both drugs). The reported comparative metabolomic analysis revealed a very different metabolic profile between Ptac2S and cisplatin treated samples, thus confirming the different mechanism of action of Ptac2S also in the Epithelial Ovarian Carcinoma (EOC), SKOV-3 cells line. In particular, higher levels of pyruvate were observed in Ptac2S treated, with respect to cisplatin treated, cells (in both aqueous and culture media). In addition, a very different lipid expression resulted after the exposure to the two drugs (Ptac2S and cisplatin). These results suggest a possible explanation for the Ptac2S ability to circumvent cisplatin resistance in SKOV-3 cells.
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 dosedependent 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.
Thanks to recent advances in analytical technologies and statistical capabilities, the application field of metabolomics has increased significantly. Currently, this approach is used to investigate biological substrates looking for metabolic profile alterations, diseases markers, and drug effects. In particular, NMR spectroscopy has shown great potential as a detection technique, mainly for the ability to detect multiple (10s to 100s) metabolites at once without separation. Only in recent years has the NMR-based metabolomic approach been extended to investigate the cell metabolic alterations induced by metal-based antitumor drug administration. As expected, these studies are mainly focused on platinum complexes, but some palladium and ruthenium compounds are also under investigation. The use of a metabolomics approach was very effective in assessing tumor response to drugs and providing insights into the mechanism of action and resistance. Therefore, metabolomics may open new perspectives into the development of metal-based drugs. In particular, it has been shown that NMR-based, in vitro metabolomics is a powerful tool for detecting variations of the cell metabolites induced by the metal drug exposure, thus offering also the possibility of identifying specific markers for in vivo monitoring of tumor responsiveness to anticancer treatments.
Extensive application of agrochemicals for crop production and protection has negatively affected soil health, crop productivity, and the environment. Organic amendments have been proposed as an efficient alternative for enhancing soil and plant health. Vermicompost amendment offers a sustainable approach to plant nutrition, improving soil health and fertility. This review aims to provide key insights into the potential of vermicompost to boost crop production and protect crops from biotic and abiotic stresses without harming the environment. The role played by earthworms in improving organic matter decomposition, soil fertility, and soil microorganisms’ activity is also discussed here. The value of vermicompost is its promotion of plant growth based on its enrichment with all essential nutrients, beneficial microbes, and plant growth hormones. This review analyzes how vermicompost regulates plant growth and its role in mitigating abiotic stresses such as soil salinity and drought, as well as biotic stresses such as diseases and insect pests attack. The beneficial effects of hormones and humic substances present in vermicompost are also discussed in this review. In fact, due to its properties, vermicompost can be a good substitute for chemical fertilizers and pesticides and its usage could contribute to producing healthy, contaminant-free food for the growing population without negatively affecting the environment.
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