Fibroblasts transfection by electroporation in 3D reconstructed human dermal tissue.

The understanding of the mechanisms involved in DNA electrotransfer in human skin remains modest and limits the clinical development of various biomedical applications, such as DNA vaccination. To elucidate some mechanisms of DNA transfer in the skin following electroporation, we created a model of the dermis using a tissue engineering approach. This model allowed us to study the electrotransfection of fibroblasts in a three-dimensional environment that included multiple layers of fibroblasts as well as the self-secreted collagen matrix.

Skin electroporation for transdermal drug delivery: Electrical measurements, numerical model and molecule delivery.

Skin electroporation for drug delivery involves the application of Pulsed Electric Fields (PEFs) on the skin to disrupt its barrier function in a temporary and non-invasive manner, increasing the uptake of drugs. It represents a potential alternative to delivery methods that are invasive (e.g.

Cancer Imaging by Intravital Microscopy: The Dorsal Window Chamber Model.

Intravital microscopy allows a direct visualization of cells' behavior in their environment in a living organism with all its complexity. With appropriated models, longitudinal studies of structural and functional changes can be followed in the same animal on long period. In the field of cancer, the dorsal window chamber model is the model of choice for tumor events such as cells migration, vessels growth, and their permeability or interactions between cells and vessels.

Therapeutic perspectives of high pulse repetition rate electroporation.

Electroporation, a technique that uses electrical pulses to temporarily or permanently destabilize cell membranes, is increasingly used in cancer treatment, gene therapy, and cardiac tissue ablation. Although the technique is efficient, patients report discomfort and pain. Current strategies that aim to minimize pain and muscle contraction rely on the use of pharmacological agents.

Effects of Nanosecond Pulsed Electric Field (nsPEF) on a Multicellular Spheroid Tumor Model: Influence of Pulse Duration, Pulse Repetition Rate, Absorbed Energy, and Temperature.

Cellular response upon nsPEF exposure depends on different parameters, such as pulse number and duration, the intensity of the electric field, pulse repetition rate (PRR), pulsing buffer composition, absorbed energy, and local temperature increase. Therefore, a deep insight into the impact of such parameters on cellular response is paramount to adaptively optimize nsPEF treatment. Herein, we examined the effects of nsPEF ≤ 10 ns on long-term cellular viability and growth as a function of pulse duration (2-10 ns), PRR (20 and 200 Hz), cumulative time duration (1-5 µs), and absorbed electrical energy density (up to 81 mJ/mm in sucrose-containing low-conductivity buffer and up to 700 mJ/mm in high-conductivity HBSS buffer).

Gene Electrotransfer Efficiency in 2D and 3D Cancer Cell Models Using Different Electroporation Protocols: A Comparative Study.

Electroporation, a method relying on a pulsed electric field to induce transient cell membrane permeabilization, can be used as a non-viral method to transfer genes in vitro and in vivo. Such transfer holds great promise for cancer treatment, as it can induce or replace missing or non-functioning genes. Yet, while efficient in vitro, gene-electrotherapy remains challenging in tumors.

Hydrogels with electrically conductive nanomaterials for biomedical applications.

Hydrogels, soft 3D materials of cross-linked hydrophilic polymer chains with a high water content, have found numerous applications in biomedicine because of their similarity to native tissue, biocompatibility and tuneable properties. In general, hydrogels are poor conductors of electric current, due to the insulating nature of commonly-used hydrophilic polymer chains. A number of biomedical applications require or benefit from an increased electrical conductivity.

Imaging of the skin microvascularization using spatially depolarized dynamic speckle.

Significance: We propose a technique devoted to real-time high-resolution imaging of skin microvascularization.

Aim: The process utilizes the temporal variation of the spatially depolarized optical speckle field generated by moving red blood cells when illuminated with fully polarized coherent light.

Approach: Polarimetric filtering prevents the contribution of surface scattering from reaching the camera and thus favors the detection of multiscattered photons from the deeper layers of the skin.

Transdermal Delivery of Macromolecules Using Two-in-One Nanocomposite Device for Skin Electroporation.

Delivery of hydrophilic molecules through the skin using electroporation is a promising alternative approach to intradermal injection. Recently, we developed a two-in-one electrode/reservoir material composed of carbon nanotubes and agarose hydrogel. In this work, we evaluated the potential of the device to achieve non-invasive transdermal drug delivery using skin electroporation.

High Power Electromagnetic Waves Exposure of Healthy and Tumor Bearing Mice: Assessment of Effects on Mice Growth, Behavior, Tumor Growth, and Vessel Permeabilization.

High power radiofrequencies may transiently or permanently disrupt the functioning of electronic devices, but their effect on living systems remains unknown. With the aim to evaluate the safety and biological effects of narrow-band and wide-band high-power electromagnetic (HPEM) waves, we studied their effects upon exposure of healthy and tumor-bearing mice. In field experiments, the exposure to 1.

Transfer of small interfering RNA by electropermeabilization in tumor spheroids.

The ability to modulate deregulated genes by RNAi provides treatment perspectives in certain diseases including cancers. Electrotransfer of oligonucleotides was studied in vitro, showing a direct transfer of negatively charged siRNA across the plasma membrane into the cytoplasm. In vivo, the feasibility of siRNA electrotransfer was demonstrated in different studies and tissues.

A nanosecond pulsed electric field (nsPEF) can affect membrane permeabilization and cellular viability in a 3D spheroids tumor model.

Three-dimensional (3D) cellular models represent more realistically the complexity of in vivo tumors compared to 2D cultures. While 3D models were largely used in classical electroporation, the effects of nanosecond pulsed electric field (nsPEF) have been poorly investigated. In this study, we evaluated the biological effects induced by nsPEF on spheroid tumor model derived from the HCT-116 human colorectal carcinoma cell line.

Electric Field Based Therapies in Cancer Treatment.

Enormous progress has been made in pulsed electric field-based therapies since J [...

Anti-Cancer Potential of Two Plasma-Activated Liquids: Implication of Long-Lived Reactive Oxygen and Nitrogen Species.

Cold atmospheric plasma-exposed culture medium may efficiently kill cancer cells in vitro. Due to the complexity of the medium obtained after plasma exposure, less complex physiological liquids, such as saline solutions and saline buffers, are gathering momentum. Among the plethora of reactive oxygen and nitrogen species (RONS) that are produced in these plasma-activated liquids, hydrogen peroxide, nitrite and nitrate appear to be mainly responsible for cytotoxic and genotoxic effects.

Development of a near infrared protein nanoprobe targeting Thomsen-Friedenreich antigen for intraoperative detection of submillimeter nodules in an ovarian peritoneal carcinomatosis mouse model.

The epithelial ovarian cancer is one of the most lethal gynecological malignancy due to its late diagnostic and many relapses observed after first line of treatment. Once diagnose, the most important prognostic factor is the completeness of cytoreductive surgery. To achieve this goal, surgeons have to pinpoint and remove nodules, especially the smallest nodules.

Magnetic Silica-Coated Iron Oxide Nanochains as Photothermal Agents, Disrupting the Extracellular Matrix, and Eradicating Cancer Cells.

Cancerous cells and the tumor microenvironment are among key elements involved in cancer development, progression, and resistance to treatment. In order to tackle the cells and the extracellular matrix, we herein propose the use of a class of silica-coated iron oxide nanochains, which have superior magnetic responsiveness and can act as efficient photothermal agents. When internalized by different cancer cell lines and normal (non-cancerous) cells, the nanochains are not toxic, as assessed on 2D and 3D cell culture models.

Cyclin B1 knockdown mediated by clinically approved pulsed electric fields siRNA delivery induces tumor regression in murine melanoma.

RNA interference (RNAi) represents a promising therapy for the specific inhibition of gene expression in targeted tissues including tumors. To realize the therapeutic potential of RNAi drugs, non-immunogenic, efficient, and tissue-specific delivery technologies must be developed. We have previously shown that pulsed electric field (PEF) can deliver siRNAs into tumor cells thanks to long electrophoretic drift occurring during the use of millisecond duration pulses.

Evaluations of Acute and Sub-Acute Biological Effects of Narrowband and Moderate-Band High Power Electromagnetic Waves on Cellular Spheroids.

High power electromagnetic signals can disrupt the functioning of electronic devices. As electromagnetism plays a role in cells homeostasis, such electromagnetic signals could potentially also alter some physiological processes. Herein we report on distinct biological parameters assessment after cellular spheroids exposure to high power electromagnetic signals, such as the ones used for defense applications.

Biodistribution and Biosafety of a Poly(Phosphorhydrazone) Dendrimer, an Anti-Inflammatory Drug-Candidate.

Dendrimers are nanosized, arborescent polymers of which size and structure are perfectly controlled. This is one reason why they are widely used for biomedical purposes. Previously, we showed that a phosphorus-based dendrimer capped with anionic azabisphosphonate groups (so-called ABP dendrimer) has immuno-modulatory and anti-inflammatory properties towards human immune cells in vitro.

Tumor cells educate mesenchymal stromal cells to release chemoprotective and immunomodulatory factors.

Factors released by surrounding cells such as cancer-associated mesenchymal stromal cells (CA-MSCs) are involved in tumor progression and chemoresistance. In this study, we characterize the mechanisms by which naïve mesenchymal stromal cells (MSCs) can acquire a CA-MSCs phenotype. Ovarian tumor cells trigger the transformation of MSCs to CA-MSCs by expressing pro-tumoral genes implicated in the chemoresistance of cancer cells, resulting in the secretion of high levels of CXC chemokine receptors 1 and 2 (CXCR1/2) ligands such as chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL2, and interleukin 8 (IL-8).

Pre-clinical investigation of the synergy effect of interleukin-12 gene-electro-transfer during partially irreversible electropermeabilization against melanoma.

Background: Melanoma is a very aggressive skin tumor that can be cured when diagnosed and treated in its early stages. However, at the time of identification, the tumor is frequently in a metastatic stage. Intensive research is currently ongoing to improve the efficacy of the immune system in eliminating cancer cells.

Pulsed Electric Field Treatment Enhances the Cytotoxicity of Plasma-Activated Liquids in a Three-Dimensional Human Colorectal Cancer Cell Model.

Cold atmospheric plasma and more recently, plasma-activated liquids (culture media, water or buffered solutions previously exposed to plasma), are gathering momentum in cancer cells treatment. Nevertheless, in vitro tests show that this novel approach is sometimes less efficient than expected. We here evaluate the mechanisms of action of the plasma-activated PBS and suggest to use electropermeabilization (EP) in combination with the plasma-activated phosphate-buffered saline (PBS), in order to potentiate the cytotoxic effect of the plasma activated liquid.

Elucidation of in vitro cellular steps induced by antitumor treatment with plasma-activated medium.

Numerous studies have reported cold atmospheric plasma cytotoxic activities in various cancer cell lines, either by direct exposure to non-thermal plasma or indirectly by activating a medium (plasma-activated medium, PAM) prior to cell treatment. We suggested the use of in vitro 3D tumor model spheroids to determine the potential of PAM for cancer therapy at the tissue scale, especially in human tumor tissue. This work aimed to better understand the effect of PAM on human colorectal tumor spheroids by describing the in vitro-induced-cell death kinetics and associated mechanisms to further improve its therapeutic potential.

Overview of Carbon Nanotubes for Biomedical Applications.

The unique combination of mechanical, optical and electrical properties offered by carbon nanotubes has fostered research for their use in many kinds of applications, including the biomedical field. However, due to persisting outstanding questions regarding their potential toxicity when considered as free particles, the research is now focusing on their immobilization on substrates for interface tuning or as biosensors, as load in nanocomposite materials where they improve both mechanical and electrical properties or even for direct use as scaffolds for tissue engineering. After a brief introduction to carbon nanotubes in general and their proposed applications in the biomedical field, this review will focus on nanocomposite materials with hydrogel-based matrices and especially their potential future use for diagnostics, tissue engineering or targeted drug delivery.