.

A nanoparticle-based system, composed of the gallium(III) complex of a minimally substituted corrole that is coated by transferrin as a targeting vehicle ( NPs), has been used for pre-clinical evaluation of its efficacy against human metastatic castration-resistant prostate cancer (mCRPC) tumor xenografts. All mice ( = 9) responded to a dose of 10 mg/kg, with a remarkable tumor growth inhibition of 400% following 2 weeks of treatment; Ames and hERG tests excluded potential concerns regarding mutagenicity and cardiotoxicity, respectively. Also demonstrated is the potential application of these NPs as sonodynamic agents for the preclinical treatment of pancreatic cancer.

A Synthetic SOD/Catalase Mimic Compound for the Treatment of ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons. To date, the etiology of the disease is still unclear, with evidence of reactive oxygen species, mitochondrial dysfunction, iron homeostasis perturbation, protein misfolding and protein aggregation as key players in the pathology of the disease. Twenty percent of familial ALS and two percent of sporadic ALS instances are due to a mutation in Cu/Zn superoxide dismutase (SOD1).

Protein-coated corrole nanoparticles for the treatment of prostate cancer cells.

Development of novel therapeutic strategies to eradicate malignant tumors is of paramount importance in cancer research. In a recent study, we have introduced a facile protocol for the preparation of corrole-protein nanoparticles (NPs). These NPs consist of a corrole-core coated with protein.

Corroles and corrole/transferrin nanoconjugates as candidates for sonodynamic therapy.

We report the utility of water-soluble corroles and also protein-coated nanoparticles (NPs) of lipophilic corroles as potent candidates for sonodynamic therapy (SDT), through the detection and quantification of the singlet oxygen that is produced by the ultrasonic irradiation of their aqueous solutions. Preliminary results on a cancer cell line provide evidence for the true utility of the NPs for SDT.

Structures and Spectroscopic Properties of Metallocorrole Nanoparticles.

In aqueous media, hydrophobic metallocorroles form nanoparticles that are potential theranostic anticancer agents. We have analyzed the electronic and Raman spectra of Al(III), Ga(III), and Au(III) corrole nanoparticles (and made comparisons with DFT-validated assignments of the IR spectra of corresponding monomers) in order to estimate the strengths of corrole-corrole electronic couplings in these assemblies. We find that these spectra are virtually unchanged upon aggregation, confirming that the intermolecular interactions in these nanoparticles are very weak.

Cell-Penetrating Protein/Corrole Nanoparticles.

Recent work has highlighted the potential of metallocorroles as versatile platforms for the development of drugs and imaging agents, since the bioavailability, physicochemical properties and therapeutic activity can be dramatically altered by metal ion substitution and/or functional group replacement. Significant advances in cancer treatment and imaging have been reported based on work with a water-soluble bis-sulfonated gallium corrole in both cellular and rodent-based models. We now show that cytotoxicities increase in the order Ga < Fe < Al < Mn < Sb < Au for bis-sulfonated corroles; and, importantly, that they correlate with metallocorrole affinities for very low density lipoprotein (VLDL), the main carrier of lipophilic drugs.

One-Pot Synthesis of Contracted and Expanded Porphyrins with meso-CF Groups.

Corrole and sapphyrin with the smallest meso-substituents reported so far were prepared in a one-pot synthesis that relies on a non-aldehydic precursor for introducing CF groups. The substantial amounts of products obtained by this facile pathway allowed for the full characterization of 5,10,15-tris(trifluoromethyl)corrole, the access to a variety of stable chelates thereof and investigations that disclose the unique structural and chemical properties induced by the CF substituents. The novel 5,10,15,20-tetra(trifluoromethyl)sapphyrin undergoes only single protonation, which according to its crystal structure is stabilized by favorable non-bonding F/H interaction between the meso-CF and the inverted pyrrolic NH.

One-Pot Conversion of Fluorophores to Phosphorophores.

Facile, one-pot conversion of free base 5,10,15-tris(pentafluorophenyl)corrole, (H)tpfc, into the coinage metal complexes of 2,3,17,18-tetraiodo-5,10,15-tris(pentafluorophenyl)corrole, (I-tpfc)M (M = Cu, Ag, Au), is reported. The iodination/metalation procedures provide much higher yields and larger selectivity than both conceivable stepwise syntheses. Photophysical analysis shows that the gold(III) complex (I-tpfc)Au displays phosphorescence at room temperature and a substantial quantum yield for singlet oxygen formation.

Neurorescue by a ROS Decomposition Catalyst.

The effect of the bis-sulfonated iron(III) corrole (1-Fe), a potent decomposition catalyst of reactive oxygen species, on rescuing SN4741 cells that were damaged by 6-hydroxydopamine (6-OHDA) was investigated as an in vitro model system for studying cell death of dopaminergic neurons in the substantia nigra. Important findings that accompanied the ability to rescue dopaminergic neurons were increased expression of phenotypic dopaminergic proteins, such as tyrosine hydroxylase (TH) and dopamine transporter (DAT), which were significantly depleted upon 6-OHDA-mediated damage. 1-Fe also elevated expression levels of aldehyde dehydrogenase 1 (ALDH-1), previously disclosed as a cardinal protein in the pathogenesis of Parkinson's disease.