1,3,6-Trigalloylglucose: A Novel Potent Anti-Helicobacter pylori Adhesion Agent Derived from Aqueous Extracts of Terminalia chebula Retz.

1,3,6-Trigalloylglucose is a natural compound that can be extracted from the aqueous extracts of ripe fruit of Terminalia chebula Retz, commonly known as "Haritaki". The potential anti-Helicobacter pylori (HP) activity of this compound has not been extensively studied or confirmed in scientific research. This compound was isolated using a semi-preparative liquid chromatography (LC) system and identified through Ultra-high-performance liquid chromatography-MS/MS (UPLC-MS/MS) and Nuclear Magnetic Resonance (NMR). Its role was evaluated using Minimum inhibitory concentration (MIC) assay and minimum bactericidal concentration (MBC) assay, scanning electron microscope (SEM), inhibiting kinetics curves, urea fast test, Cell Counting Kit-8 (CCK-8) assay, Western blot, and Griess Reagent System. Results showed that this compound effectively inhibits the growth of HP strain ATCC 700392, damages the HP structure, and suppresses the Cytotoxin-associated gene A (Cag A) protein, a crucial factor in HP infection. Importantly, it exhibits selective antimicrobial activity without impacting normal epithelial cells GES-1. In vitro studies have revealed that 1,3,6-Trigalloylglucose acts as an anti-adhesive agent, disrupting the adhesion of HP to host cells, a critical step in HP infection. These findings underscore the potential of 1,3,6-Trigalloylglucose as a targeted therapeutic agent against HP infections.

Se/Ru-Decorated Porous Metal-Organic Framework Nanoparticles for The Delivery of Pooled siRNAs to Reversing Multidrug Resistance in Taxol-Resistant Breast Cancer Cells.

We report here a novel and personalized strategy of selenium/ruthenium nanoparticles modified metal organic frameworks MIL-101(Fe) for delivering pooled small interfering RNAs (siRNAs) to enhance therapy efficacy by silencing multidrug resistance (MDR) genes and interfere with microtubule (MT) dynamics in MCF-7/T (Taxol-resistance) cell. The existence of coordinatively unsaturated metal sites in MIL-101(Fe) can strongly interact with the electron-rich functional groups of cysteine, which can be regarded as the linkage between selenium/ruthenium nanoparticles and MIL-101(Fe). Se@MIL-101 and Ru@MIL-101 loaded with MDR gene-silencing siRNAs via surface coordination can significantly enhance protection of siRNAs against nuclease degradation, increase siRNA cellular uptake, and promote siRNA escape from endosomes/lysosome to silence MDR genes in MCF-7/T cell, resulting in enhanced cytotoxicity through the induction of apoptosis with the signaling pathways of phosphorylation of p53, MAPK, and PI3K/Akt and the dynamic instability of MTs and disrupting normal mitotic spindle formation. Furthermore, in vivo investigation of the nanoparticles on nude mice bearing MCF-7/T cancer xenografts confirmed that Se@MIL-101-(P+V)siRNA nanoparticles can significantly enhance cancer therapeutic efficacy and decrease systemic toxicity in vivo.

Investigation of functional selenium nanoparticles as potent antimicrobial agents against superbugs.

Developing highly effective antibacterial agents is important for a wide range of applications. However, the emergence of multiple antibiotic-resistant bacteria poses a public health threat. Many developed agents have limited practical application due to chemical instability, low biocompatibility, and poor long-term antibacterial efficiency. In the following study, we synthesize a synergistic nanocomposite by conjugating quercetin (Qu) and acetylcholine (Ach) to the surface of Se nanoparticles (Qu-Ach@SeNPs). Quercetin has been reported to exhibit a wide range of biological activities related to their antibacterial activity and acetylcholine as a neurotransmitter, which can combine with the receptor on the bacterial cell. Arrows indicate NPs and arrowheads indicate compromised cell walls. The study demonstrated how Qu-Ach@SeNPs exhibit a synergistically enhanced antibacterial performance against the multidrug-resistant superbugs (MDRs) compared to Qu@SeNPs and Ach@SeNPs alone. Qu-Ach@SeNPs are effective against MDRs, such as Methicillin-resistant Staphylococcus aureus (MRSA), at a low dose. The mechanistic studies showed that Qu-Ach@SeNPs attach to the bacterial cell wall, causing irreversible damage to the membrane, and thereby achieving a remarkable synergistic antibacterial effect to inhibit MRSA. The findings suggested that the synergistic properties of quercetin and acetylcholine enhance the antibacterial activity of SeNPs. In this way, Qu-Ach@SeNPs comprise a new class of inorganic nano-antibacterial agents that can be used as useful applications in biomedical devices. STATEMENT OF SIGNIFICANCE: The Qu-Ach@SeNPs have low cytotoxicity when tested on normal human cells in vitro. Qu-Ach@SeNPs are effective against MDRs, such as Methicillin-resistant S. aureus (MRSA), at a low dose. Importantly, Qu-Ach@SeNPs showed no emergence of resistance. These results suggest that Qu-Ach@SeNPs have excellent antibacterial activities. These agents can serve as good antibacterial agents against superbugs. Our data suggest that these antibacterial agents may have widespread application in the field of medicine for combating infectious diseases caused by MDRs, as well as other infectious diseases.

Co-delivery of Se nanoparticles and pooled SiRNAs for overcoming drug resistance mediated by P-glycoprotein and class III ß-tubulin in drug-resistant breast cancers.

Drug resistance mediated by P-glycoprotein (P-gp) and class III ß-tubulin (ß-tubulin III) is a major barrier in microtubule-targeting cancer chemotherapy. In this study, layered double hydroxide nanoparticles (LDHs) were employed to simultaneously deliver selenium (Se) and pooled small interfering RNAs (siRNAs) to achieve therapeutic efficacy. LDH-supported Se nanoparticles (Se@LDH) were compacted with siRNAs (anti-P-gp and anti-ß-tubulin III) via electrostatic interactions, which could protect siRNA from degradation. Se@LDH showed excellent abilities to deliver siRNA into cells, including enhancing siRNA internalization, and promoting siRNA escape from endosomes. siRNA transfection experiments further confirmed a higher gene silencing efficiency of Se@LDH than LDH. Interestingly, we found Se@LDH may be a microtubule (MT) stabilizing agent which could inhibit cell proliferation by blocking cell cycle at G2/M phase, disrupting normal mitotic spindle formation and inducing cell apoptosis. When complexed with different specific siRNAs, Se@LDH/siRNA nanoparticles, especially the Se@LDH-pooled siRNAs, exhibit an efficient gene-silencing effect that significantly downregulate the expression of P-gp and ß-tubulin III. Moreover, Se@LDH-pooled siRNAs could induce cell apoptosis, change cell morphology and increase cellular ROS levels through change the expression of Bcl-2/Bax, activation of caspase-3, PI3K/AKT/mTOR and MAPK/ERK pathways. These results suggested that co-delivery of Se and pooled siRNAs may be a promising strategy for overcoming the drug resistance mediated by P-gp and ß-tubulin III in drug-resistant breast cancers.

Multifunctional selenium nanoparticles: Chiral selectivity of delivering MDR-siRNA for reversal of multidrug resistance and real-time biofluorescence imaging.

Herein, chiral selenium nanoparticles (L-SeNPs/D-SeNPs) modified with a dinuclear Ruthenium (II) complex were used to effectively deliver siRNA targeting the MDR1 gene. In this co-delivery system, the luminescent dinuclear Ruthenium (II) complex was developed to act as a gene carrier and anti-tumor drug, while offering luminescent imaging to follow the intracellular trafficking. Interestingly, Ru@L-SeNPs exhibited a stronger protein and pDNA affinity than Ru@D-SeNPs, indicating that chirality may have an effect on pDNA/siRNA binding and biocompatibility. Cisplatin-resistant A549R cells treated with Ru@L-SeNPs-siRNA demonstrated significant downregulation of P-glycoprotein (P-gp) expression, resulting in unprecedented enhanced cytotoxicity through the induction of apoptosis with the involvement of phosphorylation of p53, MAPK and PI3K/Akt signaling pathways. In vivo investigation confirmed that Ru@L-SeNPs-siRNA nanoparticles exhibited high tumor-targeted fluorescence, enhanced anti-tumor efficacy, and decreased systemic toxicity. These results suggest that Ru@L-SeNPs are promising vectors for the delivery of siRNA and for real-time tracking of treatment. FROM THE CLINICAL EDITOR: In this study, the authors designed bi-functional selenium nanoparticles with specific chirality to deliver siRNA, for targeting tumor MDR1 gene. The underlying ruthenium (II) complex could also offer fluorescence for real-time imaging. This new system has been shown to have enhanced efficacy against drug resistant tumor cells in both in-vitro and in-vivo experiments.