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Systemic toxicity and severe side effects are commonly associated with anticancer chemotherapies. New strategies based on enhanced drug selectivity and targeted delivery to cancer cells while leaving healthy tissue undamaged can reduce the global patient burden. Herein, we report the design, synthesis and characterization of a bio-inspired hybrid multifunctional drug delivery system based on diatom microalgae. The microalgae’s surface was chemically functionalized with hybrid vitamin B12-photoactivatable molecules and the materials further loaded with highly active rhenium(I) tricarbonyl anticancer complexes. The constructs showed enhanced adherence to colorectal cancer (CRC) cells and slow release of the chemotherapeutic drugs. The overall toxicity of the hybrid multifunctional drug delivery system was further enhanced by photoactivation of the microalgae surface. Depending on the construct and anticancer drug, a 2-fold increase in the cytotoxic efficacy of the drug was observed upon light irradiation. The use of this targeted drug delivery strategy, together with selective spatial–temporal light activation, may lead to lower effective concentration of anticancer drugs, thereby reducing medication doses, possible side effects and overall burden for the patient.

Gold(iii) complexes with different l-histidine-containing dipeptides, [Au(Gly-l-His-N,N,N3)Cl]Cl·3HO (1a), [Au(Gly-l-His-N,N,N3)Cl]NO·1.25HO (1b), [Au(l-Ala-l-His-N,N,N3)Cl][AuCl]·HO (2a), [Au(l-Ala-l-His-N,N,N3)Cl]NO·2.5HO (2b), [Au(l-Val-l-His-N,N,N3)Cl]Cl·2HO (3), [Au(l-Leu-l-His-N,N,N3)Cl]Cl (4a) and [Au(l-Leu-l-His-N,N,N3)Cl][AuCl]·HO (4b), have been synthesized and structurally characterized by spectroscopic (H NMR, IR and UV-vis) and single-crystal X-ray diffraction techniques. The antimicrobial efficiency of these gold(iii) complexes, along with K[AuCl] and the corresponding dipeptides, was evaluated against the broad panel of Gram-positive and Gram-negative bacteria and fungi, displaying their moderate inhibiting activity. Moreover, the cytotoxic properties of the investigated complexes were assessed against the normal human lung fibroblast cell line (MRC5) and two human cancer, cervix (HeLa) and lung (A549) cell lines. None of the complexes exerted significant cytotoxic activity; nevertheless complexes that did show selectivity in terms of cancer vs. normal cell lines (2a/b and 4a/b) have been evaluated using zebrafish (Danio rerio) embryos for toxicity and antiangiogenic potential. Although the gold(iii) complexes achieved an antiangiogenic effect comparable to the known angiogenic inhibitors auranofin and sunitinib malate at 30-fold higher concentrations, they had no cardiovascular side effects, which commonly accompany auranofin and sunitinib malate treatment. Finally, binding of the gold(iii) complexes to the active sites of both human and bacterial (Escherichia coli) thioredoxin reductases (TrxRs) was demonstrated by conducting a molecular docking study, suggesting that the mechanism of biological action of these complexes can be associated with their interaction with the TrxR active site.

Gold(III) complexes with 1,7- and 4,7-phenanthroline ligands, [AuCl(1,7-phen-κN7)] (1) and [AuCl(4,7-phen-κN4)] (2) were synthesized and structurally characterized by spectroscopic (NMR, IR and UV-vis) and single-crystal X-ray diffraction techniques. In these complexes, 1,7- and 4,7-phenanthrolines are monodentatedly coordinated to the Au(III) ion through the N7 and N4 nitrogen atoms, respectively. In comparison to the clinically relevant anti-angiogenic compounds auranofin and sunitinib, gold(III)-phenanthroline complexes showed from 1.5- to 20-fold higher anti-angiogenic potential, and 13- and 118-fold lower toxicity. Among the tested compounds, complex 1 was the most potent and may be an excellent anti-angiogenic drug candidate, since it showed strong anti-angiogenic activity in zebrafish embryos achieving IC value (concentration resulting in an anti-angiogenic phenotype at 50% of embryos) of 2.89μM, while had low toxicity with LC value (the concentration inducing the lethal effect of 50% embryos) of 128μM. Molecular docking study revealed that both complexes and ligands could suppress angiogenesis targeting the multiple major regulators of angiogenesis, such as the vascular endothelial growth factor receptor (VEGFR-2), the matrix metalloproteases (MMP-2 and MMP-9), and thioredoxin reductase (TrxR1), where the complexes showed higher binding affinity in comparison to ligands, and particularly to auranofin, but comparable to sunitinib, an anti-angiogenic drug of clinical relevance.

Mononuclear silver(I) complexes with 1,7-phenanthroline (1,7-phen), [Ag(NO-O,O') (1,7-phen-N7)] (1) and [Ag(1,7-phen-N7)]X, X = ClO (2), CFSO (3), BF (4) and SbF (5) were synthesized and structurally characterized by NMR (H and C), IR and UV-Vis spectroscopy and ESI mass spectrometry. The crystal structures of 1, 3 and 4 were determined by single-crystal X-ray diffraction analysis. In all these complexes, 1,7-phen coordinates to the Ag(I) ion in a monodentate fashion via the less sterically hindered N7 nitrogen atom. The investigation of the solution stability of 1-5 in DMSO revealed that they are sufficiently stable in this solvent at room temperature. Complexes 1-5 showed selectivity towards Candida spp. in comparison to bacteria, effectively inhibiting the growth of four different Candida species with minimal inhibitory concentrations (MIC) between 1.2 and 11.3 μM. Based on the lowest MIC values and the lowest cytotoxicity against healthy human fibroblasts with selectivity index of more than 30, the antifungal potential was examined in detail for the complex 1. It had the ability to attenuate C. albicans virulence and to reduce epithelial cell damage in the cell infection model. Induction of reactive oxygen species (ROS) response has been detected in C. albicans, with fungal DNA being one of the possible target biomolecules. The toxicity profile of 1 in the zebrafish model (Danio rerio) revealed improved safety and activity in comparison to that of clinically utilized silver(I) sulfadiazine.

Sulfonamides represent the oldest synthetic antibacterial agents; however, their central position in controlling bacterial diseases has been seriously damaged by the development of widespread resistance. Hereby, we revisited sulfathiazole, a...