Bioinorganic Chemistry and Applications

Nowadays, the search for new chemotherapeutic agents with low toxicity and high selectivity is a major concern. In this paper, we report the synthesis and characterization of a hybrid thiosemicarbazone/hydrazone ligand in its neutral form (L¹H₂) and as the chloride salt ([L¹H₃]Cl)-, three diorganotin (IV) complexes, and one complex with Sn (IV). The compounds have been fully characterized by IR, mass spectra, ¹H, ¹³C, and ¹¹⁹Sn NMR, ¹¹⁹Sn CP/MAS NMR, and by single crystal X-ray diffraction. The organotin compounds have the empirical formula [SnR₂L¹] (R = Me, Bu, and Ph), but in the solid state, they are polymeric species with seven coordination number due to weak coordination of the pyridine nitrogen, whereas in solution, the polymeric structure is lost to afford hexacoordinate monomeric species. Reaction with SnI₄ yields complex [Sn (L¹)₂]·EtOH, with the metal in a distorted dodecahedral arrangement. We have evaluated the antiproliferative activity of the two forms of the ligands and the four coordination compounds against MDA-MB-231, HeLa, PC3, and HepG2 cancer cell lines, and WI-38 normal cell line, and all the compounds present higher activity than cisplatin, used as the standard control. To investigate the mode of action, we have selected the most active complex, containing phenyl substituents, and used the triple negative breast cancer cell line MDA-MB-231. The results show that the complex induces apoptotic cell death promoted by generation of reactive oxygen species and by disruption of mitochondrial membrane potential.

Carrier system therapies based on combining cancer drugs with nanoparticles have been reported to control tumor growth and significantly reduce the side effects of cancer drugs. We thought that paclitaxel-loaded silver nanoparticles (AgNPs-PTX) were the right carrier to target cancer cells. We also carried out antimicrobial activity experiments as systems formed with nanoparticles have been shown to have antimicrobial activity. In our study, we used easy-to-synthesize and low-cost silver nanoparticles (AgNPs) with biocatalytic and photocatalytic advantages as drug carriers. We investigated the antiproliferative activities of silver nanoparticles synthesized by adding paclitaxel on MCF-7 (breast adenocarcinoma cell line), A549 (lung carcinoma cell line), C6 (brain glioma cell line) cells, and healthy WI-38 (fibroblast normal cell line) cell lines and their antimicrobial activities on 10 different microorganisms. The synthesized AgNPs and AgNPs-PTX were characterized by dynamic light scattering (DLS), scanning transmission electron microscopy, UV-visible spectroscopy, Fourier transform infrared spectroscopy, and X-ray spectroscopy. The nanoparticles were spherical in shape, with AgNPs ranging in size from 2.32 to 5.6 nm and AgNPs-PTXs from 24.36 to 58.77 nm. AgNPs demonstrated well stability of −47.3 mV, and AgNPs-PTX showed good stability of −25.4 mV. The antiproliferative effects of the synthesized nanoparticles were determined by XTT (tetrazolium dye; 2,3-bis-(2-methoxy-4-nitro-5-sulfenyl)-(2H)-tetrazolium-5-carboxanilide), and the proapoptotic effects were determined by annexin V/propidium iodide (PI) staining. The effect of AgNPs-PTX was more effective, and anticancer activity was higher than PTX in all cell lines. When selectivity indices were calculated, AgNPs-PTX was more selective in the A549 cell line (SI value 6.53 μg/mL). AgNPs-PTX was determined to increase apoptosis cells by inducing DNA fragmentation. To determine the antimicrobial activity, the MIC (minimum inhibitory concentration) test was performed using 8 different bacteria and 2 different fungi. Seven of the 10 microorganisms tested exhibited high antimicrobial activity according to the MIC ≤100 μg/mL standard, reaching MIC values below 100 μg/mL and 100 μg/mL for both AgNPs and AgNPs-PTX compared to reference sources. Compared to standard antibiotics, AgNPs-PTX was highly effective against 4 microorganisms.

Photodynamic therapy (PDT) has received increasing attention for tumor therapy due to its minimal invasiveness and spatiotemporal selectivity. However, the poor targeting of photosensitizer and hypoxia of the tumor microenvironment limit the PDT efficacy. Herein, eccentric hollow mesoporous organic silica nanoparticles (EHMONs) are prepared by anisotropic encapsulation and hydrothermal etching for constructing PDT nanoplatforms with targeting and hypoxia-alleviating properties. The prepared EHMONs possess a unique eccentric hollow structure, a uniform size (300 nm), a large cavity, and ordered mesoporous channels (2.3 nm). The EHMONs are modified with the mitochondria-targeting molecule triphenylphosphine (CTPP) and photosensitizers chlorin e6 (Ce6). Oxygen-carrying compound perfluorocarbons (PFCs) are further loaded in the internal cavity of EHMONs. Hemolytic assays and in vitro toxicity experiments show that the EHMONs-Ce6-CTPP possesses very good biocompatibility and can target mitochondria of triple-negative breast cancer, thus increasing the accumulation of photosensitizers Ce6 at mitochondria after entering cancer cells. The EHMONs-Ce6-CTPP@PFCs with oxygen-carrying ability can alleviate hypoxia after entering in the cancer cell. Phantom and cellular experiments show that the EHMONs-Ce6-CTPP@PFCs produce more singlet oxygen reactive oxygen species (ROSs). Thus, in vitro and in vivo experiments demonstrated that the EHMONs-Ce6-CTPP@PFCs showed excellent treatment effects for triple-negative breast cancer. This research provides a new method for a targeting and oxygen-carrying nanoplatform for enhancing PDF effectiveness.

Purpose. The crystal adhesion caused by the damage of renal tubular epithelial cells (HK-2) is the key to the formation of kidney stones. However, no effective preventive drug has been found. This study aims to explore the recovery effects of four Laminaria polysaccharides (SLPs) with different sulfate (–OSO₃^–) contents on damaged HK-2 cells and the difference in the adhesion of damaged cells to nanometer calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) before and after recovery. Methods. Sodium oxalate (2.6 mmol/L) was used to damage HK-2 cells to establish a damaged model. SLPs (LP0, SLP1, SLP2, and SLP3) with –OSO₃^– contents of 0.73%, 15.1%, 22.8%, and 31.3%, respectively, were used to restore the damaged cells, and the effects of SLPs on the adhesion of COM and COD, with a size of about 100 nm before and after recovery, were measured. Results. The following results were observed after SLPs recovered the damaged HK-2 cells: increased cell viability, restored cell morphology, decreased reactive oxygen levels, increased mitochondrial membrane potential, decreased phosphatidylserine eversion ratio, increased cell migration ability, reduced expression of annexin A1, transmembrane protein, and heat shock protein 90 on the cell surface, and reduced adhesion amount of cells to COM and COD. Under the same conditions, the adhesion ability of cells to COD crystals was weaker than that to COM crystals. Conclusions. As the sulfate content in SLPs increases, the ability of SLPs to recover damaged HK-2 cells and inhibit crystal adhesion increases. SLP3 with high –OSO₃^– content may be a potential drug to prevent kidney stones.

Objective. This study aimed to investigate the growth of calcium oxalate (CaOx) crystals regulated by Auricularia auricular polysaccharides (AAPs) with different viscosity-average molecular weights (), the toxicity of AAP-regulated CaOx crystals toward HK-2 cells, and the prevention and treatment capabilities of AAPs for CaOx stones. Methods. The scavenging capability and reducing capacity of four kinds of AAPs ( of 31.52, 11.82, 5.86, and 3.34 kDa) on hydroxyl, ABTS, and DPPH free radicals and their capability to chelate divalent iron ions were detected. AAP-regulated CaOx crystals were evaluated by using zeta potential, thermogravimetric analysis, X-ray diffraction, and scanning electron microscopy. The cytotoxicity of AAP-regulated crystals was evaluated through examination of cell viability, cell death, malondialdehyde (MDA) content, and cell surface hyaluronic acid (HA) expression. Results. The in vitro antioxidant activities of the four AAPs were observed in the following order: AAP0 < AAP1 < AAP2 < AAP3. Thus, AAP3, which had the smallest , had the strongest antioxidant activity. AAPs can inhibit the growth of CaOx monohydrate (COM), induce the formation of CaOx dihydrate (COD), and reduce the degree of crystal aggregation, with AAP3 exhibiting the strongest capability. Cell experiments showed the lowest cytotoxicity in AAP3-regulated CaOx crystals, along with the lowest MDA content, HA expression, and cell mortality. In addition, COD presented less cytotoxicity than COM. Meanwhile, the cytotoxicity of blunt crystals was less than that of sharp crystals. Conclusion. AAPs, particularly AAP3, showed an excellent antioxidative capability in vitro, and AAP3-regulated CaOx crystals presented minimal cytotoxicity.

Investigating and synthesizing potent antibacterial NPs using biological methods is highly preferred, and it involves nontoxic, cost-effective, and environmentally friendly chemicals and methods. Antibiotic drug resistance and oxidative stress have become a serious public health issue worldwide. Hence, the key objective of this study was to biologically synthesize and characterize the potent antibacterial Co₃O₄@ZnO core-shell nanoparticles for the antibacterial application. The radical scavenging ability of green synthesized Co₃O₄@ZnO core-shell nanoparticles was also determined. In this study, Co₃O₄@ZnO core-shell nanoparticles (CZCS NPs) have been synthesized using three different core to shell materials ratios of Co₃O₄ to ZnO (0.5 : 0.25 CZCS (1), 0.5 : 0.5 CZCS (2), and 0.5 : 0.75 M CZCS (3)) by employing Datura stramonium leaf extract. The polycrystalline nature of Co₃O₄@ZnO core-shell nanoparticles was investigated using the XRD and SAED characterization techniques. The investigated nanostructure of Co₃O₄@ZnO core-shell nanoparticles appeared with Co₃O₄ as the core and ZnO as an outer shell. Additionally, a variety of physicochemical properties of the nanoparticles were determined using various characterization techniques. The average crystallite sizes of CZCS (1), CZCS (2), and CZCS (3) were found to be , , and  nm, respectively. The band gap energy values for CZCS (1), CZCS (2), and CZCS (3) determined from the UV-DRS data were found to be 2.75, 2.76, and 2.73 eV, respectively. The high inhibition activities against S. aureus, S. pyogenes, E. coli, and P. aeruginosa bacterial strains were obtained for the small size CZCS (2) nanoparticles at the concentration of 100 mg/mL with 22 ± 0.34, 19 ± , 18 ± , and 17 ± .32 mm values, respectively. The high inhibition performance of CZCS (2) nanoparticles against Gram-positive and Gram-negative bacteria which is even above the control drug ampicillin is because of its small size and synergistic effect. The percentage scavenging activity of Co₃O₄@ZnO core-shell nanoparticles was also studied and CZCS (2) nanoparticles showed a good scavenging capacity (86.87%) at 500 μg/mL with IC50 of 209.26 μg/mL.