Gene Electrotransfer via Conductivity-Clamped Electric Field Focusing Pivots Sensori-Motor DNA Therapeutics: "A Spoonful of Sugar Helps the Medicine Go Down".

Viral vectors and lipofection-based gene therapies have dispersion-dependent transduction/transfection profiles that thwart precise targeting. The study describes the development of focused close-field gene electrotransfer (GET) technology, refining spatial control of gene expression. Integration of fluidics for precise delivery of "naked" plasmid deoxyribonucleic acid (DNA) in sucrose carrier within the focused electric field enables negative biasing of near-field conductivity ("conductivity-clamping"-CC), increasing the efficiency of plasma membrane molecular translocation.

MOF-derived cobalt-iron containing nanocomposite with cascade-catalytic activities for multimodal synergistic tumor therapy.

Reactive oxygen species (ROS)-driven chemodynamic therapy has emerged as a promising anti-tumor strategy. However, the insufficient hydrogen peroxide (HO) supply in tumor microenvironment results in a low Fenton reaction rate and subsequently poor ROS production and therapeutic efficacy. Herein, we report on a new nanocomposite MIL-53@ZIF-67/S loaded with doxorubicin and glucose oxidase, which is decomposed under the acidic tumor microenvironment to release Fe, Co, glucose oxidase, and doxorubicin.

Antibiotic-Free Gene Vectors: A 25-Year Journey to Clinical Trials.

Until very recently, the major use, for gene therapy, specifically of linear or circular DNA, such as plasmids, was as ancillary products for viral vectors' production or as a genetic template for mRNA production. Thanks to targeted and more efficient physical or chemical delivery techniques and to the refinement of their structure, non-viral plasmid DNA are now under intensive consideration as pharmaceutical drugs. Plasmids traditionally carry an antibiotic resistance gene for providing the selection pressure necessary for maintenance in a bacterial host.

H O -Induced Persistent Luminescence Signal Enhancement Applied to Biosensing.

Persistent luminescence nanoparticles (PLNPs) are innovative materials able to emit light for a long time after the end of their excitation. Thanks to this property, their detection can be separated in time from the excitation, making it possible to obtain images with a high signal-to-noise ratio. This optical property can be of particular interest for the development of in vitro biosensors.

Carbopol dispersed PAA-modified UIO-66 with high colloidal stability as a combination nano-adjuvant boosts immune response and protection against pseudorabies virus in mice and pigs.

Although inactivated vaccines have higher safety than live-attenuated vaccines in the control of pseudorabies virus (PRV), their protection efficacy is limited due to insufficient immunogenicity when used alone. High-performance adjuvants that can potentiate immune responses are highly desirable to improve the protection efficacy of inactivated vaccines. In this work, we have developed U@PAA-Car, a Carbopol dispersed zirconium-based metal-organic framework UIO-66 modified by polyacrylic acid (PAA), as a promising adjuvant for inactivated PRV vaccines.

Liposome Biodistribution via Europium Complexes.

Vector biodistribution is a requirement prior pharmaceutical development. Radioactive tracers allow the most sensitive and quantitative assessment of biodistribution, and conventional fluorophores are widely used in academic laboratories. We propose here to use europium complexes as a label for nanoparticles or biotherapeutics taking liposomes as models.

GMP-Grade Manufacturing and Quality Control of a Non-Virally Engineered Advanced Therapy Medicinal Product for Personalized Treatment of Age-Related Macular Degeneration.

The introduction of new therapeutics requires validation of Good Manufacturing Practice (GMP)-grade manufacturing including suitable quality controls. This is challenging for Advanced Therapy Medicinal Products (ATMP) with personalized batches. We have developed a person-alized, cell-based gene therapy to treat age-related macular degeneration and established a vali-dation strategy of the GMP-grade manufacture for the ATMP; manufacturing and quality control were challenging due to a low cell number, batch-to-batch variability and short production duration.

Fate and biological impact of persistent luminescence nanoparticles after injection in mice: a one-year follow-up.

Persistent luminescence nanoparticles (PLNPs) are attracting growing interest for non-invasive optical imaging of tissues with a high signal to noise ratio. PLNPs can emit a persistent luminescence signal through the tissue transparency window for several minutes, after UV light excitation before systemic administration or directly through visible irradiation, allowing us to get rid of the autofluorescence signal of tissues. PLNPs constitute a promising alternative to the commercially available optical near infrared probes thanks to their versatile functionalization capabilities for improvement of the circulation time in the blood stream.

A hollow CoCuS with glutathione depleting and photothermal properties for synergistic dual-enhanced chemodynamic/photothermal cancer therapy.

Chemodynamic therapy has become an emerging cancer treatment strategy, in which tumor cells are killed through toxic reactive oxygen species (ROS), especially hydroxyl radicals (˙OH) produced by the Fenton reaction. Nevertheless, low ROS generation efficiency and ROS depletion by cellular antioxidant systems are still the main obstacles in chemodynamic therapy. In the present work, we propose a dually enhanced chemodynamic therapy obtained by inhibiting ˙OH consumption and promoting ˙OH production based on the administration of bimetallic sulfide CoCuS nanoparticles functionalized by polyethylene glycol.

Combination of thermal ablation by focused ultrasound, pFAR4-IL-12 transfection and lipidic adjuvant provide a distal immune response.

Aim: Gene-based immunotherapy against cancer is limited by low gene transfer efficiency. In the literature, interleukin-12 (IL-12) encoding plasmid associated with sonoporation has been shown to enhance antitumoral activity. Moreover, non-viral carriers and high-frequency ultrasound have both been shown to promote immune response activation.

A tale of two robots: Operating times and learning curves in robot-assisted lumbar fusion.

Robotic assistance technologies are being incorporated into minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) to minimize radiation exposure to the patient and operating staff. However, they introduce new issues including increased operating time and difficult incorporation into surgical workflow. This study, conducted with 42 patients under the care of one neurosurgeon in Sydney, Australia, investigates the operating time increase with three different robotic modalities, and the learning curves they pose to the surgeon.

Persistent luminescence nanoparticles functionalized by polymers bearing phosphonic acid anchors: synthesis, characterization, and behaviour.

Optical imaging has become a widely used technique and is still under development for clinical diagnostics and treatment applications. For further development of the field, researchers have put much effort into the development of inorganic nanoparticles (NPs) as imaging probes. In this trend, our laboratory developed ZnGaOCr (ZGO) nanoparticles, which can emit a bright persistent luminescence signal through the tissue transparency window for dozens of minutes and can be activated with visible irradiation.

Cationic lipid nanoparticle production by microfluidization for siRNA delivery.

Microfluidization has been investigated as a new, scalable, and basic component saving method to produce cationic lipid nanoparticles, in particular for the delivery of short interfering RNAs (siRNAs). The design of experiment (DoE) allowed to reach optimized characteristics in terms of nanocarrier size reduction and low polydispersity. The structure of cationic liposomes and siRNA-lipoplexes was characterized.

Viscous Core Liposomes Increase siRNA Encapsulation and Provides Gene Inhibition When Slightly Positively Charged.

Since its discovery, evidence that siRNA was able to act as an RNA interference effector, led to its acceptation as a novel medicine. The siRNA approach is very effective, due to its catalytic mechanism, but still the limitations of its cellular delivery should be addressed. One promising form of non-viral gene delivery system is liposomes.

PLGA Based Nanospheres as a Potent Macrophage-Specific Drug Delivery System.

Macrophages possess an innate ability to scavenge heterogenous objects from the systemic circulation and to regulate inflammatory diseases in various organs via cytokine production. That makes them attractive targets for nanomedicine-based therapeutic approaches to inflammatory diseases. In the present study, we have prepared several different poly(lactic-co-glycolic acid) (PLGA) polymer nanospheres for macrophage-targeted drug delivery using both nanoprecipitation and emulsification solvent evaporation methods.

Electroporation-Based Genetic Modification of Primary Human Pigment Epithelial Cells using the Sleeping Beauty Transposon System.

Our increasingly aging society leads to a growing incidence of neurodegenerative diseases. So far, the pathological mechanisms are inadequately understood, thus impeding the establishment of defined treatments. Cell-based additive gene therapies for the increased expression of a protective factor are considered as a promising option to medicate neurodegenerative diseases, such as age-related macular degeneration (AMD).

Coating Persistent Luminescence Nanoparticles With Hydrophilic Polymers for Imaging.

Persistent luminescence nanoparticles (PLNPs) are innovative nanomaterials highly useful for bioimaging applications. Indeed, due to their particular optical properties, i.e.

Polymer Nanomedicines with Ph-Sensitive Release of Dexamethasone for the Localized Treatment of Inflammation.

Polymer-drug conjugates have several advantages in controlled drug delivery to inflammation as they can accumulate and release the drug in inflamed tissues or cells, which could circumvent the shortcomings of current therapy. To improve the therapeutic potential of polymer-drug conjugates in joint inflammation, we synthesized polymer conjugates based on -(2-hydroxypropyl) methacrylamide) copolymers labeled with a near-infrared fluorescent dye and covalently linked to the anti-inflammatory drug dexamethasone (DEX). The drug was bound to the polymer via a spacer enabling pH-sensitive drug release in conditions mimicking the environment inside inflammation-related cells.

Reduced Heterochromatin Formation on the pFAR4 Miniplasmid Allows Sustained Transgene Expression in the Mouse Liver.

Non-viral gene delivery into the liver generally mediates a transient transgene expression. A comparative analysis was performed using two gene vectors, pFAR4 and pKAR4, which differ by the absence or presence of an antibiotic resistance marker, respectively. Both plasmids carried the same eukaryotic expression cassette composed of a sulfamidase (Sgsh) cDNA expressed from the human alpha antitrypsin liver-specific promoter.

Degenerate-disc infection study with contaminant control (DISC): a multicenter prospective case-control trial.

Background: A bacterial cause of disc degeneration has evoked several controversies and, if true, would lead to a major shift in treatment paradigm. Earlier studies analyzing the relationship of bacterial disc infection within a degenerative cohort featured prolonged cultures susceptible to contamination. The degenerate-disc infection study with contaminant control (DISC) trial aims to investigate this theory further by examining infection rates using a non-degenerative control cohort in comparison to a degenerative internal control cohort and a sham cohort (sampling only sterile paraspinal tissue).

Drug repurposing in rare diseases: Myths and reality.

While nearly 8000 rare diseases have been identified, only 5 percent have licensed treatments. As most of these diseases are life threatening, it underscores the urgent need for new drugs. Drug repurposing (also called drug repositioning) consists in identifying new uses for approved or investigational drugs that are outside the scope of the original medical indication.

Kinetic and structural characterization of therapeutic albumin chemical functionalization using complementary mass spectrometry techniques.

Protein conjugates such as antibody-drugs conjugates (ADCs) represents the next generation of therapeutic proteins. They allow to combine the biological properties of the protein format with the characteristics of the conjugated ligands. The reaction implemented to couple ligands to the peptide backbone represents a crucial aspect of the production of protein conjugates, influencing the nature and the heterogeneity of the conjugates obtained.