Phthalocyanine photosensitizers (PSs) have shown promise in fluorescence imaging and photodynamic therapy (PDT) of malignant tumors, but their practical application is limited by the aggregation-induced quenching (AIQ) and inherent photobleaching of PSs. Herein, we report the synthesis of a two-dimensional nanoscale covalent organic framework (nCOF) with staggered (AB) stacking of zinc-phthalocyanines (ZnPc), ZnPc-PI, for fluorescence imaging and mitochondria-targeted PDT. ZnPc-PI isolates and confines ZnPc PSs in the rigid nCOF to reduce AIQ, improve photostability, enhance cellular uptake, and increase the level of reactive oxygen species (ROS) generation via mitochondrial targeting. ZnPc-PI shows efficient tumor accumulation, which allowed precise tumor imaging and nanoparticle tracking. With high cellular uptake and tumor accumulation, intrinsic mitochondrial targeting, and enhanced ROS generation, ZnPc-PI exhibits potent PDT efficacy with >95% tumor growth inhibition on two murine colon cancer models without causing side effects.

Nanoscale Covalent Organic Framework with Staggered Stacking of Phthalocyanines for Mitochondria-Targeted Photodynamic Therapy.

The active transport of nanoparticles into solid tumors through transcytosis has been recognized as a promising way to enhance tumor accumulation and penetration, but the effect of the physicochemical properties of nanoparticles remains unclear. Herein, we develop a type of single-molecule dual imaging nanodot by divergent growth of perylenediimide (PDI)-dye-cored polylysine dendrimers and internal orthogonal conjugation of Gd(III)-based macrocyclic probes for fluorescence imaging and magnetic resonance imaging (MRI) of surface chemistry-dependent tumor entrance. The MRI and fluorescence imaging show that sixth-generation nanodots with acetylated (G6-Ac) and oligo ethylene glycol (G6-OEG) surfaces exhibit similar high tumor accumulation but different intratumor distribution. Cellular uptake and transport experiments suggest that G6-Ac nanodots have lower lysosomal entrapment (61% vs. 83%) and a higher exocytotic rate (47% vs. 29%) than G6-OEG. Therefore, G6-Ac is more likely to undergo intercellular transport through cell transcytosis, and is able to reach a tumor area distant from blood vessels, while G6-OEG mainly enters the tumor through enhanced permeability and retention (EPR) effect-based passive transport, and is not able to deliver to distant tumor areas. This study suggests that it is possible to boost the tumor entrance of nanoparticles by engineering surface chemistry for active transport.

Surface chemistry mediates the tumor entrance of nanoparticles probed using single-molecule dual-imaging nanodots.

Dye-cored polylysine dendrimer as luminescent nanoplatform for imaging-guided anticancer drug delivery.

Candida albicans is the most common human fungal pathogen that has developed extensive virulence factors which allows successful colonization and infection of the host. Anti-virulence agents can alleviate the pathogenesis of fungi and help the immune system to eradicate them easily. This study aimed to explore the anti-virulence effect of domperidone and candesartan against C. albicans standard strain. Sub-inhibitory concentrations (1/4 and 1/8 of minimum inhibitory concentration) of domperidone and candesartan significantly inhibited the virulence factors hemolysin, lipase, protease, phospholipase, and bioflim formation. It was found that candesartan inhibited biofilm formation by 60.48–67.91%, hemolysin activity (61.21–74.14%), phospholipase activity (40–49.67%), lipase activity (58.97–73%), and protease activity (52.63%), while domperidone was found to inhibit biofilm formation by 70.54–77.49%, hemolysin activity (64.84–69.84%), phospholipase activity (49.67–60%), lipase activity (50–54.87%), and protease activity (52.63–57.9%). Quantitative real time-PCR confirmed the anti-virulence activity of domperidone and candesartan as both drugs significantly reduce the expression of the virulence genes SAP2, SAP6, PLB1, PLB2, LIP4, LIP5. In conclusion, domperidone and candesartan could serve as anti-virulence agents for treatment of C. albicans infections.

Impeding Virulence of Candida albicans by Candesartan and Domperidone

Background Proton-pump inhibitors, along with a prokinetic agent, are widely used to provide symptomatic relief amongst patients with acid peptic disease (APD). This article evaluates the effectiveness and safety of the omeprazole–domperidone combination amongst patients with type 2 diabetes mellitus for the management of APD. Methods PRIDE-2 (PRoton-pump Inhibitor in patients with type 2 DiabEtes mellitus) is a retrospective study reviewing electronic medical records of patients with type 2 diabetes mellitus and APD who were receiving the omeprazole–domperidone combination and visiting multiple Indian healthcare settings between March 2018 and April 2021. The effectiveness outcome of the therapy was evaluated in terms of resolution of APD symptoms at visit 5 (120 days after baseline visit) compared with visit 1 (baseline visit). Safety was determined in terms of reported adverse events (AEs) during the treatment period (120 days). Results A total of 174 patients were included in the study. The mean age of the patients was 51.5±9.6 years, with the majority (59.8%) being men. A significant proportion of patients reported relief from APD symptoms, including abdominal pain (91.6%), epigastric burning (68.7%), nausea (89.5%), flatulence (100.0%), loss of appetite (93.6%), and altered bowel movements (94.7%) (p<0.001 for each) at visit 5 compared with visit 1. No serious AEs were reported. Conclusion Omeprazole–domperidone combination was beneficial in providing symptomatic relief to patients with diabetes and APD. The combination therapy was well tolerated, with few reports of minor AEs.

https://www.drugsincontext.com/wp-content/uploads/2023/02/dic.2022-10-3.pdf

A real-world retrospective study of omeprazole–domperidone combination in managing acid peptic disease with PRoton-pump Inhibitors in patients with type 2 DiabEtes mellitus (PRIDE-2)

Fluorescent imaging with fluorophores has become a powerful way to explore complex biological systems and visualize nanoparticles for drug delivery. However, it is challenging to develop fluorophores with ideal physical and optical properties. We report a method to synthesize cyanine nanodots with single-molecule structure, well-defined particle size, customizable fluorescent spectrum, bright and stable fluorescence. These cyanine nanodots are acquired by the divergent synthesis of cyanine dyes-cored polylysine (PLL) dendrimers. We demonstrated the feasibility of the method by synthesizing cyanine 3 (Cy3), cyanine 5 (Cy5), or cyanine 7 (Cy7) cored single-molecule nanodots up to eight generations with a size around 11 nm. We show these cyanine nanodots are capable of multiple biomedical applications, including multicolor cellular tracing and cancer imaging. These cyanine nanodots possess many merits of organic dots and quantum dots that are promising for future application.

Molecularly Precise, Bright, Photostable, and Biocompatible Cyanine Nanodots as Alternatives to Quantum Dots for Biomedical Applications.

OBJECTIVE To find out the effects of domperidone in combination with omeprazole in the treatment of chronic superficial gastritis (CSG). METHODS Ninety-six patients who suffered from CSG and received treatment in the Binzhou People's Hospital from July 2013 to July 2014 were selected as research subjects. They were divided into a control group (48 cases) and a test group (48 cases) using double blind method. Patients in the control group were treated by omeprazole, while patients in the observation group were treated by domperidone in combination with omeprazole. The clinical effects of the two groups were observed and analyzed. RESULTS The scores of symptoms had no significant difference between the two groups before treatment. The improvement of the scores of symptoms in the test group was superior to that in the control group after treatment (P<0.05). The overall response rate of the test group was 97.92% (47/48), higher than that of the control group (75.00%). After treatment, the repair effect of gastric mucosa and the postoperative recurrence rate in the test group were superior to those of the control group (P<0.05). CONCLUSION Domperidone in combination with omeprazole can achieve ideal effect in the treatment of CSG, which is of great significance to the treatment and prognosis of patients.

Effects of domperidone in combination with omeprazole in the treatment of chronic superficial gastritis.

Fluorescent imaging with fluorophores has become a powerful way to explore complex biological systems and visualize nanoparticles for drug delivery. However, it is challenging to develop fluorophores with ideal physical and optical properties. We report a method to synthesize cyanine nanodots with a single-molecule structure, well-defined particle size, customizable fluorescent spectrum, and bright and stable fluorescence. These cyanine nanodots are acquired by the divergent synthesis of cyanine-dye-cored polylysine (PLL) dendrimers. We demonstrated the feasibility of the method by synthesizing cyanine 3 (Cy3), cyanine 5 (Cy5), or cyanine 7 (Cy7) cored single-molecule nanodots up to eight generations with a size of around 11 nm. We show that these cyanine nanodots are capable of multiple biomedical applications, including multicolor cellular tracing and cancer imaging. These cyanine nanodots possess many merits of organic dots and quantum dots that are promising for future application. 

Molecularly Precise, Bright, Photostable, and Biocompatible Cyanine Nanodots as Alternatives to Quantum Dots for Biomedical Applications

Abstract Illeis bistigmosa (Mulsant, 1850) is a potential biological control agent of powdery mildews. We have determined the first mitochondrial genome of I. bistigmosa. The circular mitogenome of I. bistigmosa consists of 17,840 bp including 13 protein-coding genes, 22 tRNAs, 2 rRNAs, and a control region (D-loop). The base composition was AT-biased (78.44%). Maximum-likelihood phylogenetic trees strongly supported the monophyly of Coccinellinae. Illeis bistigmosa is the sister group of Halyzia sedecimguttata and Halyziini species (unclassified Halyziini), within fungivorous coccinellids. Illeis bistigmosa mitochondrial genome will be a fundamental resource for understanding the molecular phylogenetic relationships of the species-rich family Coccinellidae of Coleoptera.

https://www.tandfonline.com/doi/pdf/10.1080/23802359.2022.2057244?needAccess=true

Characterization of the complete mitochondrial genome of Illeis bistigmosa (Coleoptera: Coccinellidae)

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Papers

Molecularly Precise, Bright, Photostable, and Biocompatible Cyanine Nanodots as Alternatives to Quantum Dots for Biomedical Applications.

Effects of domperidone in combination with omeprazole in the treatment of chronic superficial gastritis.

Molecularly Precise, Bright, Photostable, and Biocompatible Cyanine Nanodots as Alternatives to Quantum Dots for Biomedical Applications

Characterization of the complete mitochondrial genome of Illeis bistigmosa (Coleoptera: Coccinellidae)