The potential of mesenchymal stem cell coexpressing cytosine deaminase and secretory IL18-FC chimeric cytokine in suppressing glioblastoma recurrence.

Glioblastoma multiforme (GBM) patients have a high recurrence rate of 90%, and the 5-year survival rate is only about 5%. Cytosine deaminase (CDA)/5-fluorocytosine (5-FC) gene therapy is a promising glioma treatment as 5-FC can cross the blood-brain barrier (BBB), while 5-fluorouracil (5-FU) cannot. Furthermore, 5-FU can assist reversing the immunological status of cold solid tumors.

Synthesis of manganese-incorporated polycaplactone-poly (glyceryl methacrylate) theranostic smart hybrid polymersomes for efficient colon adenocarcinoma treatment.

In the current study, a multifunctional nanoscale vesicular system (polymersome) with the ability to accumulate in the site of action, control drug release and integrate diagnostic and therapeutic functions was developed. The theranostic polymersome was engineered as a promising dual-functional nanoplatform, which can be used for tumor therapy and magnetic resonance imaging (MRI). In this regard, the amphiphilic diblock copolymer of poly(ε-caprolactone)-block-poly(glyceryl methacrylate)[(PCL-b-PGMA)] was synthesized by combined ring-opening polymerization (ROP), and reversible addition-fragmentation chain-transfer (RAFT) polymerization techniques followed by hydrolysis of the pendant oxiran rings to hydroxyl groups.

Evaluation of debridement effects of bromelain-loaded sodium alginate nanoparticles incorporated into chitosan hydrogel in animal models.

Objectives: Bromelain, a mixture of proteolytic enzymes from pineapple () is known as a potential debriding agent in burn treatment. In this research, the debridement efficiency of chitosan hydrogel loaded by sodium alginate-chitosan nanoparticles (NPs) containing bromelain (Br 10%-AG-CS NPs) was evaluated in animal models.

Materials And Methods: The NPs were prepared using the ionic gelation technique and their properties were identified.

Evaluation of the osteogenic potential of crocin-incorporated collagen scaffold on the bone marrow mesenchymal stem cells.

Objective: The present study aimed to evaluate the effect of crocin (CRO)-loaded collagen (COL) scaffold on the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BM-MSCs).

Significance: Different studies have been conducted to develop an efficient strategy to accelerate and improve the recovery process of bone defects. It was shown that CRO, extracted from saffron, could induce osteogenic differentiation of rat BM-MSCs.

Targeted doxorubicin-loaded mesenchymal stem cells-derived exosomes as a versatile platform for fighting against colorectal cancer.

Exosomes hold great potential for cancer treatment to deliver therapeutics due to its inherent low immunogenicity. Exosomes are biocompatible cell-exocytosed secreted vesicles by most cell types, which can be used to construct novel biomanufacturing platform for drug delivery and cancer therapy. In this study, we implemented nano-sized vesicles which were secreted by mesenchymal stem cell (MSC), to encapsulate doxorubicin (DOX) through electroporation method (DOX@exosome).

DNA G-quadruplexes binding and antitumor activity of palladium aryl oxime ligand complexes encapsulated in either albumin or algal cellulose nanoparticles.

The interactions between two Pd complexes, designated as [Pd(C,N-(CHC(Cl) = NO)-4)] (complex 1) and [Pd(CHC = NO)] (complex 2), with the human telomeric G-quadruplex DNA, 5'-G(TAG)-3' (HTG21), were monitored using spectroscopic, biological, and molecular modeling studies. According to the UV-vis results, these complexes can strongly induce and stabilize G-quadruplex DNA structure with K = 4.5(±0.

Effective and safe in vivo gene delivery based on polyglutamic acid complexes with heterocyclic amine modified-polyethylenimine.

Polyethylenimine (PEI) has been extensively used for non-viral gene delivery. Increasing the molecular weight of PEI often improves transfection efficiency, but enhances cytotoxicity and non-specific interaction with plasma proteins, limiting its use in clinical applications. In this study, poly-l-glutamic acid (L-PGA) as an anionic polymer, was introduced to piperazine-modified PEI to improve its in vivo properties.

Tetrac-decorated chitosan-coated PLGA nanoparticles as a new platform for targeted delivery of SN38.

New integrin-targeted nanoparticles made of chitosan-stabilized PLGA matrix was developed to specifically target colon adenocarcinoma. To this aim, SN38-encapsulated chitosan-coated PLGA NPs were conjugated with tetrac for integrin receptor-guided delivery. To provide a sustained release pattern for SN38, it was loaded into nanoparticles using single emulsion method.

Evaluation of Efficiency of Modified Polypropylenimine (PPI) with Alkyl Chains as Non-viral Vectors Used in Co-delivery of Doxorubicin and TRAIL Plasmid.

In this study, co-delivery system was achieved via plasmid encoding TNF related apoptosis inducing ligand (pTRAIL) and doxorubicin (DOX) using carrier based on polypropylenimine (PPI) modified with 10-bromodecanoic acid. Incorporation of alkylcarboxylate chain to PPIs (G4 and G5) could improve transfection efficiency via overcoming the plasma membrane barrier of the cells and decrease cytotoxicity of PPI. Characterization of fabricated NPs revealed that PPI G5 in which 30% of primary amines were substituted by alkyl carboxylate chain (PPI G5-Alkyl 30%) has higher drug loading as compared to the other formulations.

Tetrac-conjugated polymersomes for integrin-targeted delivery of camptothecin to colon adenocarcinoma in vitro and in vivo.

In this study, we prepared tetraiodothyroacetic acid (tetrac) conjugated PEG-PLGA polymersomes for the targeted delivery of camptothecin to colon adenocarcinoma. Tetrac, which binds to integrin αβ with high affinity and specificity, was covalently conjugated to the surface of the PEGylated polymersomal formulation of camptothecin (CPT). The hydrodynamic and morphological properties of the prepared system were evaluated using TEM (transmission electron microscopy), SEM (scanning electron microscopy) and DLS (dynamic light scattering) experiments.

Synthesis of theranostic epithelial cell adhesion molecule targeted mesoporous silica nanoparticle with gold gatekeeper for hepatocellular carcinoma.

Aim: In this study, we report the fabrication of epithelial cell adhesion molecule targeted 5-fluorouracil (5-FU) encapsulated PEGylated mesoporous silica nanoparticles (NPs) hybridized with gold NPs (PEG-Au@Si-5-FU) as gatekeeper for theranostic applications.

Materials & Methods: The prepared targeted and nontargeted formulations were evaluated in vitro in terms of their cellular internalization and toxicity. The prepared theranostic hybrid system was also implemented for computed tomography of HepG2 tumor-bearing nude mice in vivo.

Smart AS1411-aptamer conjugated pegylated PAMAM dendrimer for the superior delivery of camptothecin to colon adenocarcinoma in vitro and in vivo.

In the current study camptothecin-loaded pegylated PAMAM dendrimer were synthesized and were functionalized with AS1411 anti-nucleolin aptamers for site-specific targeting against colorectal cancer cells which over expresses nucleolin receptors. The morphological properties and size dispersity of the prepared nanoparticles were evaluated using transmission electron microscope (TEM) and DLS. The drug-loading content and encapsulation efficiency were obtained 8.

PAMAM-pullulan conjugates as targeted gene carriers for liver cell.

Targeted nano-carriers are highly needed to promote nucleic acid delivery into the specific cell for therapeutic approaches. Pullulan as a linear carbohydrate has an intrinsic liver targeting property interacting with asialoglycoprotein receptor (ASGPR) found on liver cells. In the present study, we developed polyamidoamine (PAMAM)-pullulan conjugates and investigated their targeting activity in delivering gene into liver cells.

Alkyl cross-linked low molecular weight polypropyleneimine dendrimers as efficient gene delivery vectors.

Objectives: In recent years, polypropyleneimine (PPI) dendrimers have attracted great interest as non-viral gene delivery systems because of their attractive features including highly branched architecture with number of reactive end groups. However, without being structurally modified, they are not efficient gene carriers. In the present study, generation 2 and 3 (G2 and G3) of PPI dendrimers were conjugated with alkylcarboxylate groups as linker to enhance the transfection efficiency while maintaining their low cell toxicity.

Comparison study of the effect of alkyl-modified and unmodified PAMAM and PPI dendrimers on solubility and antitumor activity of crocetin.

Poor water solubility of hydrophobic drugs is one of the major problems in pharmaceutical sciences. Herein, in order to address the poor solubility of crocetin, the 30% of primary amines of PAMAM G4 and PPI G4 were alkylated and evaluated as drug delivery vectors. According to the results, this modification could improve the drug delivery efficiency in term of drug solubility, release pattern and cytotoxicity; however, the encapsulation yield was decreased.

Gene delivery efficiency and cytotoxicity of heterocyclic amine-modified PAMAM and PPI dendrimers.

Poly-(amidoamine) (PAMAM) and poly-(propylenimine) (PPI) are the two most widely investigated dendrimers for drug and gene delivery. In order to enhance DNA transfection activity of these dendrimers, generation 3 and 4 PAMAM and generation 4 and 5 PPI were modified by partial substitution of surface primary amines with histidine, pyridine, and piperazine, which have buffering capacity properties. It was shown that higher dendrimer generations and higher grafting percentages (30% and 50% of primary amines) were associated with higher transfection activity.

Preparation of Effective and Safe Gene Carriers by Grafting Alkyl Chains to Generation 5 Polypropyleneimine.

Gene therapy is a novel method to treat a variety of diseases including genetic disorders and cancer. Nonviral gene carriers have now gained considerable attention as gene carrier systems. Polyamidoamine (PAMAM) and polypropyleneimine (PPI) are the two most widely used denderimers in gene delivery studies.

Effects of rutin on acrylamide-induced neurotoxicity.

Background: Rutin is an important flavonoid that is consumed in the daily diet. The cytoprotective effects of rutin, including antioxidative, and neuroprotective have been shown in several studies. Neurotoxic effects of acrylamide (ACR) have been established in humans and animals.

Arginine-rich hydrophobic polyethylenimine: potent agent with simple components for nucleic acid delivery.

Conjugation of various arginine-rich peptide sequences to vectors based on 10 kDa polyethylenimine (PEI) and its hydrophobic derivative (hexanoate-PEI) was investigated as a strategy for improving pDNA and siRNA transfection activities. Six different arginine-histidine (RH) sequences and two arginine-serine (RS) sequences with a range of R/H ratios were designed and coupled to PEI and hexanoate-PEI. All arginine-rich peptide derivatives of PEI significantly enhanced luciferase gene expression compared to PEI 10 kDa alone.

Development and Validation of HPLC Method for Determination of Crocetin, a constituent of Saffron, in Human Serum Samples.

Objective(s): The present study reports the development and validation of a sensitive and rapid extraction method beside high performance liquid chromatographic method for the determination of crocetin in human serum.

Materials And Methods: The HPLC method was carried out by using a C18 reversed-phase column and a mobile phase composed of methanol/water/acetic acid (85:14.5:0.

Molecular weight-dependent genetic information transfer with disulfide-linked polyethylenimine-based nonviral vectors.

One strategy for improving gene vector properties of polyethylenimine is to facilitate individual transfection mechanism steps. This study investigates (i) improving transfection efficiency by attaching peptide nuclear localization signals (nuclear localization signals: SV40 large T antigen nuclear localization signal or C-terminus of histone H1) to polyethylenimine (10 kDa) and (ii) using disulfide linkages, which are expected to be stable during polyplex formation, but cleaved inside cells giving improved gene release. Nuclear localization signal-containing polyplexes exhibited low cytotoxicity, whereas transfection efficiency with high molecular weight plasmid DNA increased up to 3.