A new generation of N-heterocyclic carbene (NHC) gold-selenolato complexes as potent anticancer agents: distinct synthetic routes and evaluation in 2D and 3D cancer models.

Two distinct synthetic pathways are disclosed that lead to new gold-selenolato complexes, stabilized by N-heterocyclic carbenes (NHCs). The weak base route can provide facile access to phenylselenolate complexes of gold, using both NHC and phopshine ligands. In addition, the pathway based on the carbometallation of elemental selenium enables the construction of a more diverse library of products, based on substituted aryl-selenide fragments whose selenol congeners are not commercially available.

Longitudinal prediction of drug response in high-grade serous ovarian cancer organoid cultures aligning with clinical responses.

Introduction: High-grade serous ovarian cancer (HGSOC) ranks among the most aggressive gynecological malignancies. Its high mortality is driven by frequent recurrence after primary treatments and the development of platinum resistance. Traditional drug development using animal models is time-consuming and often lacks reproducibility, making it less effective for precision cancer medicine.

Facile and green synthesis of [Pd(NHC)(η-R-allyl)Cl] complexes and their anticancer activity.

A facile and environmentally friendly method for synthesizing a range of palladium-N-heterocyclic carbene (NHC) complexes-[Pd(NHC)(η-R-allyl)Cl]-is described. This improved approach, which is based on the use of aqueous ammonia as weak base, is effectively exemplified with different NHC structures bearing R-allyl groups, achieving good to excellent yields while significantly reducing reaction times, temperature, cost, and overall environmental impact compared to previous methods. The synthesized complexes were evaluated for anticancer activity against several human cancer cell lines.

Discovery of reversible monoacylglycerol lipase (MAGL) inhibitors based on ortho-hydroxyanilide scaffold.

Monoacylglycerol lipase (MAGL) represents a key enzyme in the regulation of the endocannabinoid system and arachidonic acid signaling, emerging as a promising target for the treatment of inflammation, neurodegeneration, and cancer. Herein, we report the design, synthesis, and biological evaluation of a novel series of o-hydroxyanilide derivatives as reversible MAGL inhibitors. Starting from a known salicylketoxime scaffold, we introduced strategic modifications to reduce lipophilicity and enhance selectivity and potency.

Unraveling the Specific Recognition Between PD-L1 and Engineered CLP002 Functionalized Gold Nanostructures: MD Simulation Studies.

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.

Influence of the charge of 1,3,5-triaza-7-phosphaadamantane-based ligands on the anticancer activity of organopalladium complexes.

In this study, we report the synthesis and characterization of novel organopalladium complexes featuring 1,3,5-triaza-7-phosphaadamantane (PTA)-based ligands, including several cationic derivatives prepared as hexafluorophosphate salts to prevent halide exchange reactions. The complexes incorporate diverse organopalladium fragments-Pd(ii)-vinyl, Pd(ii)-butadienyl, Pd(ii)-allyl, Pd(ii)-imidoyl, Pd(ii)-aryl, and Pd(0)-alkene-many of which have recently shown promising antitumor activity. Most reactions proceeded rapidly at room temperature under aerobic conditions using non-anhydrous solvents.

Micro-Supercapacitors for Self-Powered Biosensors.

Although batteries are a highly popular energy source in biosensors, batteries can be an economic limitation for low-cost sensing applications and pose significant challenges in miniaturization, biocompatibility, and disposal. To surmount such issues, "self-powered sensors" gain the spotlight thanks to their energy harvesting from the environment through embedded miniaturized systems. In this review, the recent developments in self-powered devices are summarized with a specific focus on the integration of supercapacitors with sensors and biosensors.

Self-targeted nanosystem for enhanced chemodynamic cancer therapy.

Chemodynamic therapy (CDT) could have a significant potential for advancing cancer treatment the utilization of Fenton and Fenton-like reactions, which produce toxic reactive species. Nonetheless, the efficacy of CDT is constrained by the limited availability of catalyst ions capable of decomposing pre-existing intracellular HO and generating reactive oxygen species (ROS) necessary to achieve a therapeutic response. To address these limitations, a tailored strategy has been developed to enhance the efficacy of Fenton-like reactions to eradicate selectively cancer cells.

Unlocking the potential of organopalladium complexes for high-grade serous ovarian cancer therapy.

High-Grade Serous Ovarian Cancer (HGSOC) is the most common and lethal subtype of ovarian cancer, known for its high aggressiveness and extensive genomic alterations. Typically diagnosed at an advanced stage, HGSOC presents formidable challenges in drug therapy. The limited efficacy of standard treatments, development of chemoresistance, scarcity of targeted therapies, and significant tumor heterogeneity render this disease incurable with current treatment options, highlighting the urgent need for novel therapeutic approaches to improve patient outcomes.

Liposomal Formulations of Metallodrugs for Cancer Therapy.

The search for new antineoplastic agents is imperative, as cancer remains one of the most preeminent causes of death worldwide. Since the discovery of the therapeutic potential of cisplatin, the study of metallodrugs in cancer chemotherapy acquired increasing interest. Starting from cisplatin derivatives, such as oxaliplatin and carboplatin, in the last years, different compounds were explored, employing different metal centers such as iron, ruthenium, gold, and palladium.

Antibody Drug Conjugates for Cancer Therapy: From Metallodrugs to Nature-Inspired Payloads.

This review highlights significant advancements in antibody-drug conjugates (ADCs) equipped with metal-based and nature-inspired payloads, focusing on synthetic strategies for antibody conjugation. Traditional methods such us maleimide and succinimide conjugation and classical condensation reactions are prevalent for metallodrugs and natural compounds. However, emerging non-conventional strategies such as photoconjugation are gaining traction due to their milder conditions and, in an aspect which minimizes side reactions, selective formation of ADC.

Biodegradation of hydroxylated boron nitride nanoplatelets, their toxic effect and drug delivery application.

Boron nitride is extensively used in various biomedical applications and often interacting with the blood circulatory system. However, the effect of its biotransformation in blood plasma, drug delivery applications, and antitumor effects remains unclear. Herein, we synthesized hydroxylated BN nanoplatelets (-OH/BNNPs) that are used to load doxorubicin (DOX) for cancer therapy.

A carrier free delivery system of a MAGL inhibitor is effective on ovarian cancer.

Monoacylglycerol lipase (MAGL) is a promising target for cancer therapy due to its involvement in lipid metabolism and its impact on cancer hallmarks like cell proliferation, migration, and tumor progression. A potent reversible MAGL inhibitor, MAGL23, has been recently developed by our group, demonstrating promising anticancer activities. To enhance its pharmacological properties, a nanoformulation using nanocrystals coated with albumin was prepared (MAGL23AF).

In Vitro and In Vivo Evaluation of the Effects of Drug 2c and Derivatives on Ovarian Cancer Cells.

Background: The identification of novel therapeutic strategies for ovarian cancer (OC), the most lethal gynecological neoplasm, is of utmost urgency. Here, we have tested the effectiveness of the compound 2c (4-hydroxy-2,6-bis(4-nitrobenzylidene)cyclohexanone 2). 2c interferes with the cysteine-dependent deubiquitinating enzyme (DUB) UCHL5, thus affecting the ubiquitin-proteasome-dependent degradation of proteins.

Unveiling the promising anticancer activity of palladium(II)-aryl complexes bearing diphosphine ligands: a structure-activity relationship analysis.

In continuation of our previous works on the cytotoxic properties of organopalladium compounds, in this contribution we describe the first systematic study of the anticancer activity of Pd(II)-aryl complexes. To this end, we have prepared and thoroughly characterized a wide range of palladium derivatives bearing different diphosphine, aryl and halide ligands, developing, when necessary, specific synthetic protocols. Most of the synthesized compounds showed remarkable cytotoxicity towards ovarian and breast cancer cell lines, with IC values often comparable to or lower than that of cisplatin.

Dinuclear NHC-gold(I)-thiolato and -alkynyl complexes: synthesis, anticancer activity, and catalytic activity in lactonization reactions.

A series of novel dinuclear NHC-gold-thiolato and -alkynyl complexes bearing aromatic linkers were successfully synthesized by an efficient and simple synthetic route. The catalytic activity of these complexes was tested in a lactonization reaction. The reaction proceeds in high efficiency, in short reaction time and under mild conditions, and is complementary to existing methods.

Microplastic accumulation and ecological impacts on benthic invertebrates: Insights from a microcosm experiment.

Microplastic (MP) pollution poses a global concern, especially for benthic invertebrates. This one-month study investigated the accumulation of small MP polymers (polypropylene and polyester resin, 3-500 μm, 250 μg L) in benthic invertebrates and on one alga species. Results revealed species-specific preferences for MP size and type, driven by ingestion, adhesion, or avoidance behaviours.

Synergistic applications of cyclodextrin-based systems and metal-organic frameworks in transdermal drug delivery for skin cancer therapy.

This review article explores the innovative field of eco-friendly cyclodextrin-based coordination polymers and metal-organic frameworks (MOFs) for transdermal drug delivery in the case of skin cancer therapy. We critically examine the significant advancements in developing these nanocarriers, with a focus on their unique properties such as biocompatibility, targeted drug release, and enhanced skin permeability. These attributes are instrumental in addressing the limitations inherent in traditional skin cancer treatments and represent a paradigm shift towards more effective and patient-friendly therapeutic approaches.

Microfluidic production of amiodarone loaded nanoparticles and application in drug repositioning in ovarian cancer.

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.

Platinum(0)-η-1,2-()ditosylethene Complexes Bearing Phosphine, Isocyanide and -Heterocyclic Carbene Ligands: Synthesis and Cytotoxicity towards Ovarian and Breast Cancer Cells.

A wide range of platinum(0)-η-()-1,2-ditosylethene complexes bearing isocyanide, phosphine and -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.

SERS nanostructures with engineered active peptides against an immune checkpoint protein.

The immune checkpoint programmed death ligand 1 (PD-L1) protein is expressed by tumor cells and it suppresses the killer activity of CD8 T-lymphocyte cells binding to the programmed death 1 (PD-1) protein of these immune cells. Binding to either PD-L1 or PD1 is used for avoiding the inactivation of CD8 T-lymphocyte cells. We report, for the first time, Au plasmonic nanostructures with surface-enhanced Raman scattering (SERS) properties (SERS nanostructures) and functionalized with an engineered peptide (CLP002: Trp-His-Arg-Ser-Tyr-Tyr-Thr-Trp-Asn-Leu-Asn-Thr), which targets PD-L1.

Human Omental Mature Adipocytes used as Paclitaxel Reservoir for Cell-Based Therapy in Ovarian Cancer.

Primary human omental adipocytes and ovarian cancer(OC) cells establish a bidirectional communication in which tumor driven lipolysis is induced in adipocytes and the resulting fatty acids are delivered to cancer cells within the tumor microenvironment. Despite meaningful improvement in the treatment of OC, its efficacy is still limited by hydrophobicity and untargeted effects related to chemotherapeutics. Herein, omental adipocytes are firstly used as a reservoir for paclitaxel, named Living Paclitaxel Bullets (LPB) and secondly benefit from the established dialogue between adipocytes and cancer cells to engineer a drug delivery process that target specifically cancer cells.

Rational Design of Palladium(II) Indenyl and Allyl Complexes Bearing Phosphine and Isocyanide Ancillary Ligands with Promising Antitumor Activity.

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 ƞ and ƞ. 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.