MRI-Based Multifunctional Nanoliposomes for Enhanced HCC Therapy and Diagnosis.

The morbidity and mortality rates of hepatocellular carcinoma (HCC) are high and continue to increase. The antitumor effects of single therapies are limited because of tumor heterogeneity and drug resistance, and the lack of real-time monitoring of tumor progression during the treatment process leads to poor therapeutic outcomes. Therefore, novel nanodelivery platforms combining tumor therapy and diagnosis have garnered extensive attention.

Synthesis and antimicrobial activity evaluation of pyrazole derivatives containing imidazothiadiazole moiety.

Aim: The purpose of this work was to investigate the antimicrobial activity of pyrazole derivatives (21a - i and 23a - o) synthesized.

Materials & Methods: The pyrazole derivatives were synthesized, molecular docked and tested for their antimicrobial activity, cytotoxicity, and hemolysis rate.

Results: Most of the target compounds showed high selective inhibitory activity against multi-drug resistance compared with other strains.

Construction of GPC3-modified Lipopolymer SiRNA Delivery System.

Background: Gene therapy has been widely concerned because of its unique therapeutic mechanism. However, due to the lack of safe and effective carries, it has not been widely used in clinical practice. Glypican 3 (GPC3) is a highly specific proteoglycan for hepatocellular carcinoma and is a potential diagnostic and therapeutic target for hepatocellular carcinoma.

Synthesis and anti-liver fibrosis activity of imidazole and thiazole compounds containing amino acids.

Four series of imidazoles (15a-g, 20c, and 20d) and thiazoles (18a-g, 22a, and 22b) possessing various amino acids were synthesized and evaluated for activin receptor-like kinase 5 (ALK5) inhibitory activities in an enzymatic assay. Among them, compounds 15g and 18c showed the highest inhibitory activity against ALK5, with IC values of 0.017 and 0.

Synthesis and Antimicrobial Activity Evaluation of Pyridine Derivatives Containing Imidazo[2,1-b][1,3,4]Thiadiazole Moiety.

Four series of novel pyridine derivatives (17 a-i, 18 a-i, 19 a-e, and 20 a-e) were synthesized and their antimicrobial activities were evaluated. Of all the target compounds, almost half target compounds showed moderate or high antibacterial activity. The 4-F substituted compound 17 d (MIC=0.

Synthesis and antimicrobial activity evaluation of pyrazole derivatives containing the imidazo[2,1-b][1,3,4]thiadiazole moiety.

Four series of novel pyrazole derivatives (compounds 17a-m, 18a-m, 19a-g, and 20a-g) were synthesized, and their antibacterial and antifungal activities were evaluated. Most of the target compounds (17a-m, 18k-m, and 19b-g) showed strong antifungal activity and high selectivity relative to both Gram-positive and Gram-negative bacteria. Among them, compounds 17l (minimum inhibitory concentration [MIC] = 0.

Synthesis and Antibacterial Activity Evaluation of Imidazole Derivatives Containing 6-Methylpyridine Moiety.

A series of 2-cyclopropyl-5-(5-(6-methylpyridin-2-yl)-2-substituted-1H-imidazol-4-yl)-6-phenylimidazo[2,1-b][1,3,4]thiadiazoles (15a-t and 16a-f) were synthesized and their antibacterial activities were evaluated. More than half of the compounds showed moderate or strong antibacterial activity. Among them, compounds 15t (MIC=1-2 μg/mL) and 16d (MIC=0.

Preparation and evaluation of LA-PEG-SPION, a targeted MRI contrast agent for liver cancer.

This study aims to synthesize a magnetic resonance imaging (MRI) contrast agent that can specifically target the asialoglycoprotein receptor of liver cancer cells and evaluate its ability as a targeted MRI contrast agent. Lactobionic acid (LA) and polyethylene glycol (PEG) were used to modify superparamagnetic iron oxide nanoparticles (SPION) to obtain LA-PEG-SPION. LA-PEG-SPION was uniformly spherical under the electron microscope, with regular morphology and good dispersion.

Preparation and Preliminary Evaluation of Dual-functional Nanoparticles for MRI and siRNA Delivery.

In order to improve the transfection efficiency of gene vectors and monitor the effect of gene therapy, this study prepared a drug delivery vector with dual functions. The thiourea reaction was used to synthesize polyethyleneimine (PEI, MW: 1.8 kDa) with superparamagnetic iron oxide nanoparticles (SPION) (PEI1800-SPION), and the lipid polycationic gene vector PEI1800-SPION loaded cationic liposome (LP-PEI1800-SPION) was further prepared by ethanol injection method.

Synthesis and biological evaluation of novel benzo[c][1,2,5]thiadiazol-5-yl and thieno[3,2-c]- pyridin-2-yl imidazole derivatives as ALK5 inhibitors.

Transforming growth factor (TGF-β), a key mediator of tumor growth and metastasis, has been recognized as an important cancer drug target. A series of benzo[c][1,2,5]thiadiazol-5-yl imidazoles (14a-g) and thieno[3,2-c]-pyridin-2-yl imidazoles (20a-g) were designed, synthesized, and evaluated for their activin receptor-like kinase 5 (ALK5) activities. Among these compounds, 14c showed the highest activity (IC = 0.

MRI-visible liposome-polyethylenimine complexes for DNA delivery: preparation and evaluation.

To noninvasively monitor the effect of gene therapy and achieve an optimal therapeutic effect, liposomes encapsulated polyethylenimine (PEI)-coated superparamagnetic iron oxide nanoparticles (SPION) with dual functions of MRI diagnosis and gene therapy were prepared. SPION was synthesized via co-precipitation, and then modified with PEI via thiourea reaction. The liposomes encapsulating PEI-SPION (LP-PEI-SPION) were prepared by ethanol injection.

Lipid-Albumin Nanoparticles (LAN) for Therapeutic Delivery of Antisense Oligonucleotide against HIF-1α.

Lipid-albumin nanoparticles (LAN) were synthesized for delivery of RX-0047, an antisense oligonucleotide (ASO) against the hypoxia inducible factor-1 alpha (HIF-1α) to solid tumor. These lipid nanoparticles (LNs) incorporated a human serum albumin-pentaethylenehexamine (HSA-PEHA) conjugate, which is cationic and can form electrostatic complexes with negatively charged oligonucleotides. The delivery efficiency of LAN-RX-0047 was investigated in KB cells and a KB murine xenograft model.

CD33-Targeted Lipid Nanoparticles (aCD33LNs) for Therapeutic Delivery of GTI-2040 to Acute Myelogenous Leukemia.

CD33-targeted lipid nanoparticles (aCD33LNs) were synthesized for delivery of GTI-2040, an antisense oligonucleotide (ASO) against the R2 subunit of ribonucleotide reductase, to acute myelogenous leukemia (AML). These LNs incorporated a deoxycholate-polyethylenimine (DOC-PEI) conjugate, which has shown significant activity to facilitate oligonucleotide delivery. Anti-CD33 scFv (aCD33) was added as a targeting ligand.

Mucoadhesive and pH-sensitive thiolated Eudragit microspheres for oral delivery of Pasteurella multocida antigens containing dermonecrotoxin.

In this study, cysteine was conjugated to the Eudragit to have mucoadhesive and pH-sensitive properties. Pasteurella multocida dermonecrotoxin (PMT) is a major virulence factor as a causative agent of atrophic rhinitis (AR) in swine and, therefore, inactivated P. multocida was used as a candidate vaccine in the current study.

Intranasal immunization with plasmid DNA encoding spike protein of SARS-coronavirus/polyethylenimine nanoparticles elicits antigen-specific humoral and cellular immune responses.

Background: Immunization with the spike protein (S) of severe acute respiratory syndrome (SARS)-coronavirus (CoV) in mice is known to produce neutralizing antibodies and to prevent the infection caused by SARS-CoV. Polyethylenimine 25K (PEI) is a cationic polymer which effectively delivers the plasmid DNA.

Results: In the present study, the immune responses of BALB/c mice immunized via intranasal (i.

Degradable poly(amino ester) based on poly(ethylene glycol) dimethacrylate and polyethylenimine as a gene carrier: molecular weight of PEI affects transfection efficiency.

The aim of the research is to study the effect of polyethylenimine (PEI) molecular weight on the gene transfection efficiency of degradable poly(amino ester) based on poly(ethylene glycol) dimethacrylate (PEGDMA) and polyethylenimine (PEG-cr-PEI) as a gene carrier. Various low molecular weight (LMW) branched PEI based PEG-cr-PEI was synthesized via Michael addition. The degradation half-life of PEG-cr-PEI was longer at pH 5.

Fabrication of a novel core-shell gene delivery system based on a brush-like polycation of alpha, beta-poly (L-aspartate-graft-PEI).

Purpose: A novel core-shell gene delivery system was fabricated in order to improve its gene transfection efficiency, particularly in the presence of serum.

Materials And Methods: alpha, beta-poly (L-aspartate-graft-PEI) (PAE) was simply synthesized by ring-opening reaction of poly (L-succinimide) with low molecular weight (LMW) linear polyethylenimine (PEI, Mn = 423). PAE/DNA nanoparticles were characterized.

Synergistic anti-tumor activity of paclitaxel-incorporated conjugated linoleic acid-coupled poloxamer thermosensitive hydrogel in vitro and in vivo.

Local delivery of anti-tumor drugs provides a high local concentration and decreases the incidence of side effects commonly observed with systemic therapy. Hydrogel systems are commonly used as a local drug delivery system. In this study, we prepared a novel thermosensitive conjugated linoleic acid (CLA)-coupled poloxamer hydrogel for local delivery of paclitaxel (PTX) to gain the benefits of the pro-drug activity of the CLA-coupled poloxamer and enhanced PTX solubility due to the micellar property of the CLA-coupled poloxamer.

Mannosylated chitosan-graft-polyethylenimine as a gene carrier for Raw 264.7 cell targeting.

Gene transfer using non-viral vectors is a promising approach for the safe delivery of therapeutic genes. Among non-viral vectors, chitosans have been proposed as alternative, biocompatible cationic polymers for non-viral gene delivery. However, the low transfection efficiency and low specificity of chitosan needs to be addressed prior to clinical application.

Alpha,beta-poly(L-aspartate-graft-PEI): A pseudo-branched PEI as a gene carrier with low toxicity and high transfection efficiency.

The aim of this research is to develop a novel branched polyethylenimine (PEI)-like polycation as a potential gene carrier with high gene transfection efficiency and low toxicity. In particular, alpha,beta-poly(l-aspartate-graft-PEI) (Asp-g-PEI), a pseudo-branched PEI, was synthesized by the ring-opening reaction of poly(l-succinimide) (PSI) with low molecular weight branched PEI (LMW PEI, MW=600 and 1200). Good plasmid condensation and protection ability of Asp-g-PEI were confirmed by agarose gel electrophoresis assay.

pH-sensitive and mucoadhesive thiolated Eudragit-coated chitosan microspheres.

The aim of this study was using Eudragit-cysteine conjugate to coat on chitosan microspheres (CMs) for developing an oral protein drug delivery system, having mucoadhesive and pH-sensitive property. Bovine serum albumin (BSA) as a protein model drug was loaded in thiolated Eudragit-coated CMs (TECMs) to study the release character of the delivery system. After thiolated Eudragit coating, it was found that the release rate of BSA from BSA-loaded TECMs was observably suppressed at pH 2.

The potential of mannosylated chitosan microspheres to target macrophage mannose receptors in an adjuvant-delivery system for intranasal immunization.

A vaccine delivery system based on mannosylated chitosan microspheres (MCMs) was studied in vitro and in vivo. Bordetella bronchiseptica antigens containing dermonecrotoxin (BBD) were loaded in MCMs or chitosan microspheres (CMs). Fluorescence confocal microscopy indicated that BBD-loaded MCMs (BBD-MCMs) bound with mannose receptors on murine macrophages (RAW264.

Enhanced anticancer effect of conjugated linoleic acid by conjugation with Pluronic F127 on MCF-7 breast cancer cells.

This study is designed to evaluate whether conjugated linoleic acid-coupled Pluronic F127 (Plu-CLA) enhances anticancer efficacy in MCF-7 breast cancer cells when compared to conjugated linoleic acid (CLA) itself. CLA was simply coupled to Pluronic F127 through ester linkage between carboxyl group of CLA and hydroxyl one of Pluronic at melting state without solvent or catalyst. Plu-CLA significantly enhanced apoptosis with increasing concentration compared with CLA itself.