Engineering the protein corona: Strategies, effects, and future directions in nanoparticle therapeutics.

Nanoparticles (NPs) serve as versatile delivery systems for anticancer, antibacterial, and antioxidant agents. The manipulation of protein-NP interactions within biological systems is crucial to the application of NPs in drug delivery and cancer nanotherapeutics. The protein corona (PC) that forms on the surface of NPs is the interface between biomacromolecules and NPs and significantly influences their pharmacokinetics and pharmacodynamics. Upon encountering proteins, NPs undergo surface alterations that facilitate their clearance from circulation by the mononuclear phagocytic system (MPS). PC behavior depends largely on the biological microenvironment and the physicochemical properties of the NPs. This review describes various strategies employed to engineer PC compositions on NP surfaces. The effects of NP characteristics such as size, shape, surface modification and protein precoating on PC performance were explored. In addition, this study addresses these challenges and guides the future directions of this evolving field.

The mechanisms of action of mitochondrial targeting agents in cancer: inhibiting oxidative phosphorylation and inducing apoptosis.

The tumor microenvironment affects the structure and metabolic function of mitochondria in tumor cells. This process involves changes in metabolic activity, an increase in the amount of reactive oxygen species (ROS) in tumor cells compared to normal cells, the production of more intracellular free radicals, and the activation of oxidative pathways. From a practical perspective, it is advantageous to develop drugs that target mitochondria for the treatment of malignant tumors. Such drugs can enhance the selectivity of treatments for specific cell groups, minimize toxic effects on normal tissues, and improve combinational treatments. Mitochondrial targeting agents typically rely on small molecule medications (such as synthetic small molecules agents, active ingredients of plants, mitochondrial inhibitors or autophagy inhibitors, and others), modified mitochondrial delivery system agents (such as lipophilic cation modification or combining other molecules to form targeted mitochondrial agents), and a few mitochondrial complex inhibitors. This article will review these compounds in three main areas: oxidative phosphorylation (OXPHOS), changes in ROS levels, and endogenous oxidative and apoptotic processes.

Mifepristone Treatment in Pregnant Murine Model Induced Mammary Gland Dysplasia and Postpartum Hypogalactia.

Mammary gland dysplasia and postpartum hypogalactia often occur in humans and in the livestock breeding industry. However, their underlying mechanisms are not clear yet. Mifepristone, which has a high affinity for progesterone (P4) and glucocorticoid receptors, was exploited here to induce the disorders of mammary gland development and lactation. Four strategies were devised for treating pregnant mice with mifepristone. In the first strategy, mice were administered 1.20 mg mifepristone/kg body weight (BW) on pregnancy day 4 (Pd4). In the second strategy, mifepristone was administered to mice twice, with 1.20 mg/kg BW on Pd4 and 0.40 mg/kg BW on Pd8. In the third strategy, mice were treated with a single dose of 0.40 mg mifepristone/kg BW on Pd8. In the fourth strategy, mice were administered 0.40 mg mifepristone/kg BW on Pd8 and 0.20 mg mifepristone/kg BW on Pd12. The results suggested that mifepristone administration at the dose of 1.20 mg/kg BW on Pd4 caused significant reduction in milk production on lactation day 1 (Ld1), Ld2, and Ld3, as assessed using a weigh-suckle-weigh assay. Mammary ß-casein expression, milk yields, litter growth rates, gland structure, and serum concentrations of 17-ß estrogen (E2), P4, prolactin (PRL), growth hormone (GH), corticosterone (CORT) and oxytocin (OT) as well as the receptors of these hormones were determined during pregnancy or lactation after performing the first (Pd4) strategy. The results demonstrated that mifepristone administration during early pregnancy decreased ß-casein expression, milk yields and litter growth rates, induced fewer alveoli, enlarged alveolar lumina, and altered the levels of E2, P4, PRL, GH, CORT, and OT as well as the mRNA expression of these hormonal receptors during pregnancy or early lactation. The present study on pregnant mice treated with mifepristone offers an innovative murine model to study the mechanism underlying mammary gland dysplasia and postpartum hypogalactia.

Two star-shaped tetranuclear Ru(II) complexes containing uncoordinated imidazole groups: synthesis, characterization, photophysical and pH sensing properties.

Tetrapodal ligands H4L(1) and H4L(2) containing imidazole groups have been synthesized by the reaction of 1,10-phenanthroline-5,6-dione with 1,2,4,5-tetrakis[(4-formylphenoxy)methyl]benzene and 1,2,4,5-tetrakis[(3-formylphenoxy)methyl]benzene, respectively, in presence of NH4OAc. Two star-shaped complexes [{Ru(bpy)2}4(µ4-H4L(1))](PF6)8 and [{Ru(bpy)2}4(µ4-H4L(2))](PF6)8 (bpy = 2,2'-bipyridine) have been prepared by refluxing Ru(bpy)2Cl2 ·2H2O and each ligand in ethylene glycol. The deprotonated complexes [{Ru(bpy)2}4(µ4-L(1))](PF6)4 and [{Ru(bpy)2}4(µ4-L(2))](PF6)4 have been obtained by the reaction of sodium methoxide with [{Ru(bpy)2}4(µ4-H4L(1))](PF6)8 and [{Ru(bpy)2}4(µ4-H4L(2))](PF6)8, respectively, in methanol. The pH effects on the UV-vis light absorption and emission spectra of both complexes have been studied, and ground- and excited-state ionization constants of both complexes have been derived. The photophysical properties of both complexes are strongly dependent on the solution pH. They act as proton-induced off-on-off luminescent sensors through two successive deprotonation processes of imidazole groups, with a maximum on-off ratio of 8 in buffer solution at room temperature. Theoretical calculations for the highest occupied molecular orbital (HOMO) and lowest occupied molecular orbital (LOMO) orbitals of bridging ligand are also presented for plausible explanations of the fluorescence changes.

Two dinuclear Ru(II) polypyridyl complexes with different photophysical and cation recognition properties.

Two dinuclear Ru(II) polypyridyl complexes functionalized with vacant coordination sites have been designed and synthesized. Their photophysical properties and interactions with various metal ions have been investigated at room temperature. The two complexes exhibit different UV/Vis absorption and emission intensities. When titrated with various metal ions, complex [{Ru(bpy)2}2(µ2-L(1))](4+) exhibits a notable fluorescence quenching in the presence of Cu(2+) in H2O-CH3CN media (1:1, v/v); its analogous complex [{Ru(bpy)2}2(µ2-L(2))](4+) exhibits no cation selectivity, the fluorescence intensity of complex [{Ru(bpy)2}2(µ2-L(2))](4+) has been enhanced by several transition metal ions due to prevention of the photo-induced electron transfer process. The fluorescence titration spectra and Benesi-Hildebrand expression reveal the formation of a 1:1 bonding mode between [{Ru(bpy)2}2(µ2-L(1))](4+) and Cu(2+) ion with the association constant of 5.50×10(4) M(-1).