We synthesized superparamagnetic iron oxide nanoparticles (SPIONs), coated and functionalized with a double layer of endosomolytic polymers, polyacrylic acid (PAA) and polyethylenimine (PEI). Onto SPIONs-PAA-PEI we bound plasmid DNA carrying reporter gene for green fluorescent protein (pDNAGFP) or therapeutic gene for interleukin-12 (pDNAIL-12). Biocompatible SPIONs are suitable vectors for gene delivery via magnetofection into cells and tumors. Magnetofection of cells and tumors with pDNAGFP or pDNAIL-12, bound to SPIONs-PAA-PEI, was superior in transfection efficiency to commercially available SPIONs or lipofection, and comparable to electrically-mediated transfer. Antitumor effect was after magnetofection with pDNAIL-12, bound to SPIONs-PAA-PEI, comparable to that of electrically-mediated transfer. Magnetofection of tumors using SPIONs-PAA-PEI-pDNAIL-12 holds great potential for the further refinement aimed at cancer immuno-gene therapy since the safety and efficacy of correspondingly efficient electrically-mediated transfer is already being tested in clinical studies for gene therapy.
COBISS.SI-ID: 1237883
The article discusses the effectiveness of electrochemotherapy in treatment of breast cancer chest wall recurrences. The emphasis is on effectiveness of electrochemotherapy and possible side effects. So far electrochemotherapy has been predominantly used in treatment of melanoma metastases in the skin, however the results in treatment of chest wall breast cancer recurrences seems to be equally or even better. In fact recently electrochemotherapy has been more frequently employed at this clinical indication.
COBISS.SI-ID: 1129851
The effectiveness of gene therapy depends also on the transfection efficiency. One of the drawbacks of non-viral gene transfection methods is low transfection efficiency compared to viral vectors. this represent a specific problem especially in tumours that are histologically very heterogeneous group. The extracellular matrix degenerative enzymes hyaluronidase and collagenase have already been used for improved distribution of chemotherapeutic drugs and viral vector in tumours, however in combination and together with electroporation their use in have not been tested yet. the results of our study demonstrate that the use of combination of enzymes enables better distribution of plasmid DNA in tumours and consequently leads to better transfection efficiency especially in tumours with large amounts of extracellular matrix and high cellularity.
COBISS.SI-ID: 1136763
The aim of the study was to evaluate changes in the cytoskeleton and integrity of the monolayer of human microvascular endothelial cells (HMEC-1) in vitro after exposure to electroporation or electrochemotherapy with bleomycin. We demonstrated that exposure to electric pulses alone affects cell morphology, additional alterations were observed also for the cytoskeletal proteins F-actin and beta-tubulin. During both electroporation and electrochemotherapy, the initial phase of cellular damage was noticed at 10 min as swollen cells and honeycomb-like actin bundles. The electroporation-induced cellular effects, observed from electric pulses above 150 V, were voltage-dependent and within 24 hrs partly recoverable. The electrochemotherapy-induced cellular effects developed at 2 hrs in spindle-like cells, and more densely packed F-actin and Beta-tubulin were observed, which were dependent on the amount of bleomycin and the voltages applied. In addition, for electrochemotherapy with electric pulses above 150 V cellular changes were not recoverable within 24 hrs. The effects on monolayer integrity were reflected in the enhanced monolayer permeability, with the electrochemotherapy showing an earlier onset. We conclude that electrochemotherapy as compared to electroporation leads within 24 hrs to a quicker and more pronounced monolayer integrity damage and endothelial cell death, which together provide further insight into the cellular changes of the vascular disruption of electrochemotherapy.
COBISS.SI-ID: 1409403
The aim of the study was to evaluate the influence of DNA repair polymorphisms involved in platinum pathway on a series of 133 patients with malignant mesothelioma. Our results suggest that polymorphisms in the XPD and ERCC1 genes influence platinum-treatment efficacy, treatment response and onset of toxicity in patients.
COBISS.SI-ID: 28755417