A Strategy Utilizing Protein-Protein Interaction Hubs for the Treatment of Cancer Diseases.

We describe a strategy for the development of a rational approach of neoplastic disease therapy based on the demonstration that scale-free networks are susceptible to specific attacks directed against its connective hubs. This strategy involves the (i) selection of up-regulated hubs of connectivity in the tumors interactome, (ii) drug repurposing of these hubs, (iii) RNA silencing of non-druggable hubs, (iv) in vitro hub validation, (v) tumor-on-a-chip, (vi) in vivo validation, and (vii) clinical trial. Hubs are protein targets that are assessed as targets for rational therapy of cancer in the context of personalized oncology. We confirmed the existence of a negative correlation between malignant cell aggressivity and the target number needed for specific drugs or RNA interference (RNAi) to maximize the benefit to the patient's overall survival. Interestingly, we found that some additional proteins not generally targeted by drug treatments might justify the addition of inhibitors designed against them in order to improve therapeutic outcomes. However, many proteins are not druggable, or the available pharmacopeia for these targets is limited, which justifies a therapy based on encapsulated RNAi.

Polymeric nanoparticles as therapeutic agents against coronavirus disease.

Nanotechnology has the potential to improve the combat against life-threatening conditions. Considering the COVID-19 scenario, and future outbreaks, nanotechnology can play a pivotal role in several steps, ranging from disinfection protocols, manufacture of hospital clothes, to implementation of healthcare settings. Polymeric nanoparticles are colloidal particles with size ranging from 10 to 999 nm, composed of natural or synthetic polymers. The versatility of polymeric-based nanoparticle engineering can provide (i) specificity, (ii) tunable release kinetics, and (iii) multimodal drug composition, making it possible to overcome common limitations encountered during traditional drug development. Consequently, these particles have been widely used as drug delivery systems against several diseases, such as cancer. Due to inherent competitive advantages, polymeric-based nanoparticles hold astonishing potential to counteract the new coronavirus disease (COVID-19). For this reason, in the present study, the latest advancements in polymer-based nanotechnology approaches used to fight against SARS-CoV-2 are compiled and discussed. Moreover, the importance of forefront in vitro technologies - such as 3D bioprinting and organ-on-chip - to evaluate the efficacy of nanotherapeutic agents is also highlighted. Polymeric nanoparticles can be functionalized to enhance its potential as a nanotherapeutic agent. Due to its many advantages, polymeric-based nanoparticles systems are a promising approach against coronavirus disease 2019 (COVID-19).

Association between cationic liposomes and low molecular weight hyaluronic acid.

This work presents a study of the association between low molecular weight hyaluronic acid (16 kDa HA) and cationic liposomes composed of egg phosphatidylcholine (EPC), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). The cationic liposome/HA complexes were evaluated to determine their mesoscopic structure, average size, zeta potential, and morphology as a function of the amount of HA in the system. Small angle X-ray scattering results revealed that neighboring cationic liposomes either stick together after a partial coating of low concentration HA or disperse completely in excess of HA, but they never assemble as multilamellar vesicles. Cryo-transmission electron microscopy images confirm the existence of unilamellar vesicles and large aggregates of unilamellar vesicles for HA fractions up to 80% (w/w). High concentrations of HA (> 20% w/w) proved to be efficient for coating extruded liposomes, leading to particle complexes with sizes in the nanoscale range and a negative zeta potential.

Microfluidic devices for continuous production of pDNA/cationic liposome complexes for gene delivery and vaccine therapy.

To evaluate the process parameters for the production of plasmid DNA/cationic liposome (pDNA/CL) complexes in microfluidic systems, we studied two microfluidic devices: one with simple straight hydrodynamic flow focusing (SMD) and a second one with barriers in the mixing microchannel (patterned walls, PMD). A conventional bulk mixing method was used as a comparison to microfluidic mixing. The CL and the pDNA were combined at a molar positive/negative charge ratio of 6. The results showed that incorporating pDNA into the liposomal structures was different for the two microfluidic devices and that the temperature influenced the average size of complexes produced by the simple microfluidic device, while it did not influence the average complex size in the patterned wall device. Differences were also observed in pDNA probe accessibility in the complexes. The SMD yielded a similar quantity of non-electrostatic bound pDNA as that provided by the bulk mixing method. The complexes produced by the PMD had their pDNA probe accessibility decreased in 40% and achieved lower in vitro transfection levels in HeLa cells than the bulk mixing and simple microfluidic complexation methods. These differences are most likely due to different degrees of association between pDNA and CL, as controlled by the microfluidic devices. This study contributes to the development of rational strategies for controlling the formation of pDNA/CL complexes for further applications in gene and vaccine therapy.

Production of cyclodextrins from cornstarch granules in a sequential batch mode and in the presence of ethanol.

The influence of Toruzyme® cyclomaltodextrin glucanotransferase concentration and the presence of ethanol have been studied for the production of α-, ß-, and γ-cyclodextrins (CDs) from 15% (w/v) cornstarch, at 65 °C and pH 6, with the aim of increasing CD yield. The selected concentrations for a single batch reactor were 10% (v/v) ethanol and 0.1% (v/v) enzyme, yielding after 12 h, 37% total CDs, of which 52.2% was α-CD, 38.8% ß-CD, and 9.0% γ-CD. The enzyme specific activities per unit mass of protein for producing α-, ß-, and γ-CD were 37.25, 19.61, and 8.63 U mg(-1), respectively. Total CD yield per milliliter of enzyme was 55 g. To increase CD yield per enzyme charge and thus reduce costs, the production of CDs was tested with two sequential batches in which a single enzyme charge was used. At the end of the first batch, the enzyme was adsorbed either on 65 °C pretreated starch granules or on raw starch, and a second batch was run with this material. The best result, in this case, was obtained for pretreated starch, increasing total CD produced by 57.4%, with 53.2% α-CD, 36.1% ß-CD, and 10.7% γ-CD. CD yield per milliliter of enzyme was then 87 g.