Harnessing epigenetic inhibitors: A promising approach for overcoming challenges in pancreatic ductal adenocarcinoma treatment.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and often fatal form of malignancy frequently diagnosed at an advanced stage, posing significant challenges for treatment. The complex and intricate microenvironment of PDAC, characterized by heterogenous tumoral cells harbouring diverse mutations and epigenetic alterations, immune cells (primarily in an immunosuppressive state), cancer-associated fibroblasts (CAFs), low vascularization and extracellular matrix components supporting tumor growth, creates a physical barrier that impedes drug delivery and anti-tumoral immune cell responses, leading to therapy resistance. Despite advancements in early detection methods, and available treatments for PDAC-including surgery, radiotherapy, chemotherapy, and immunotherapy, all have shown limited efficacy.

Review and Perspectives on the Sustainability of Organic Aerogels.

Aerogels are exceptionally lightweight materials characterized by their high open porosity and remarkable specific surface area, currently used across a wide array of industrial sectors from construction to energy storage and have great potential for expanding their applicability and unlocking new market opportunities. Driven by global economic growth and an intensifying environmental crisis, there is a growing demand for engineering innovations that prioritize sustainability. Aerogels are well-positioned to support these sustainability efforts.

The Toxicity of Lead and Lead-Free Perovskite Precursors and Nanocrystals to Human Cells and Aquatic Organisms.

Halide perovskites have emerged at the forefront of semiconductor materials for photovoltaic and light-emitting devices. However, long-term stability and toxicity are the major barriers to their commercialization. In particular, the toxicity of lead (Pb) and its environmental impact have prompted the exploration of lead-free alternatives like tin (Sn) and bismuth (Bi).

Immunization with nanovaccines containing mutated K-Ras peptides and imiquimod aggravates heterotopic pancreatic cancer induced in mice.

Purpose: The growing incidence and lethality of pancreatic cancer urges the development of new therapeutic approaches. Anti-tumoral vaccines can potentiate the immune response against the tumor, targeting specific antigens expressed only on tumor cells. In this work, we designed new vaccines for pancreatic cancer, composed by chitosan nanocapsules (CS NCs) containing imiquimod (IMQ) as adjuvant, and targeting the K-Ras mutation G12V.

Gold Nanoparticles Synthesized by an Aqueous Extract of as Potential Antitumoral Enhancers of Gemcitabine.

Cancer still poses a global threat, since a lot of tumors remain untreatable despite all the available chemotherapeutic drugs, whose side effects, it must also be noted, still raise concerns. The antitumoral properties of marine seaweeds make them a potential source of new, less toxic, and more active antitumoral agents. Furthermore, these natural extracts can be combined with nanotechnology to increase their efficacy and improve targeting.

Synergistic Antitumoral Effect of Epigenetic Inhibitors and Gemcitabine in Pancreatic Cancer Cells.

Epigenetic modifications could drive some of the molecular events implicated in proliferation, drug resistance and metastasis of pancreatic ductal adenocarcinoma (PDAC). Thus, epigenetic enzyme inhibitors could be the key to revert those events and transform PDAC into a drug-sensitive tumor. We performed a systematic study with five different epigenetic enzyme inhibitors (1, UVI5008, MS275, psammaplin A, and BIX01294) targeting either Histone Deacetylase (HDAC) 1 or 1/4, DNA methyltransferase 3a (DNMT3a), Euchromatic histone lysine methyltransferase 2 (EHMT2), or Sirtuin 1 (SIRT1), as well as one drug that restores the p53 function (P53R3), in three different human PDAC cell lines (SKPC-1, MIA PaCa-2, and BxPC-3) using 2D and 3D cell cultures.

Combined Inhibition of FOSL-1 and YAP Using siRNA-Lipoplexes Reduces the Growth of Pancreatic Tumor.

Pancreatic cancer evades most of the current therapies and there is an urgent need for new treatments that could efficiently eliminate this aggressive tumor, such as the blocking of routes driving cell proliferation. In this work, we propose the use of small interfering RNA (siRNA) to inhibit the combined expression of FOSL-1 and YAP, two signaling proteins related with tumor cell proliferation and survival. To improve the efficacy of cell transfection, DODAB:MO (1:2) liposomes were used as siRNA nanocarriers, forming a complex denominated siRNA-lipoplexes.

Immunomodulatory and Antitumoral Activity of Gold Nanoparticles Synthesized by Red Algae Aqueous Extracts.

This study reports on the green and cost-efficient synthesis of gold nanoparticles from three different red algae extracts. The nanoparticles synthesized were fully characterized by UV-Vis spectroscopy, HRTEM, and Z-potential. Relevant components occurring in the extracts, such as polysaccharides or phenolic content, were assessed by analytical techniques such as spectrophotometric assays and liquid chromatography.

Improving dexamethasone drug loading and efficacy in treating arthritis through a lipophilic prodrug entrapped into PLGA-PEG nanoparticles.

Targeted delivery of dexamethasone to inflamed tissues using nanoparticles is much-needed to improve its efficacy while reducing side effects. To drastically improve dexamethasone loading and prevent burst release once injected intravenously, a lipophilic prodrug dexamethasone palmitate (DXP) was encapsulated into poly(DL-lactide-co-glycolide)-polyethylene glycol (PLGA-PEG) nanoparticles (NPs). DXP-loaded PLGA-PEG NPs (DXP-NPs) of about 150 nm with a drug loading as high as 7.

Safety and efficacy assessment of aerogels for biomedical applications.

The unique physicochemical properties of aerogels have made them an attractive class of materials for biomedical applications such as drug delivery, regenerative medicine, and wound healing. Their low density, high porosity, and ability to regulate the pore structure makes aerogels ideal nano/micro-structures for loading of drugs and active biomolecules. As a result of this, the number of in vitro and in vivo studies on the therapeutic efficacy of these porous materials has increased substantially in recent years and continues to be an area of great interest.

PAMAM dendrimers functionalised with an anti-TNF α antibody and chondroitin sulphate for treatment of rheumatoid arthritis.

Rheumatoid arthritis is a chronic autoimmune disease characterised by joint synovial inflammation, along with cartilage and bone tissue destruction. Dendrimers can offer new opportunities as drug delivery systems of molecules of interest. Herein we aimed to develop poly(amidoamine) dendrimers (PAMAM), functionalised with chondroitin sulphate (CS), lined with anti-TNF α antibodies (Abs) to provide anti-inflammatory properties.

Design of Polymeric Nanocapsules for Intranasal Vaccination against Mycobacterium Tuberculosis: Influence of the Polymeric Shell and Antigen Positioning.

Tuberculosis (TB) is the leading cause of death from a single infectious microorganism and Bacillus Calmette Guerin (BCG), the only authorized vaccine, does not confer protection against pulmonary TB. Based on the hypothesis that mucosal protection could help to prevent the infection at the site of entrance, the objective of this work was to develop an intranasal vaccine against (Mtb) the microorganism that causes TB. Our approach consisted of the use of polymeric nanocapsules (NCs) with an oily core and a polymer shell made of chitosan (CS) or inulin/polyarginine (INU/pArg).

Polymeric nanostructure vaccines: applications and challenges.

Introduction: The use of biocompatible polymers, from natural or synthetic sources, opened the door for a new era in vaccine research. These polymers offer the possibility to develop nanostructured antigen carriers that can be easily internalized by antigen-presenting cells, due to their nanometric size. Besides, the incorporation of an adjuvant allows increasing and modulating the immune response for both, polymers with or without self-adjuvant properties.

Nanoscale Lipophilic Prodrugs of Dexamethasone with Enhanced Pharmacokinetics.

The encapsulation of glucocorticoids, such as dexamethasone, in nanoparticles (NPs) faces two main issues: a low drug loading and the destabilization of the nanoparticle suspension due to drug crystallization. Here, we successfully formulated a prodrug of dexamethasone, dexamethasone palmitate (DXP), into nanoparticles stabilized by the sole presence of distearoyl- sn-glycero-3-phosphoethanolamine- N-[methoxy(poly(ethylene glycol))-2000] (DSPE-PEG). Two formulation processes, nanoprecipitation and emulsion-evaporation, allowed the formation of stable nanoparticles.

GraftFast Surface Engineering to Improve MOF Nanoparticles Furtiveness.

Controlling the outer surface of nanometric metal-organic frameworks (nanoMOFs) and further understanding the in vivo effect of the coated material are crucial for the convenient biomedical applications of MOFs. However, in most studies, the surface modification protocol is often associated with significant toxicity and/or lack of selectivity. As an alternative, how the highly selective and general grafting GraftFast method leads, through a green and simple process, to the successful attachment of multifunctional biopolymers (polyethylene glycol (PEG) and hyaluronic acid) on the external surface of nanoMOFs is reported.

Polymeric Nanocapsules for Vaccine Delivery: Influence of the Polymeric Shell on the Interaction With the Immune System.

The use of biomaterials and nanosystems in antigen delivery has played a major role in the development of novel vaccine formulations in the last few decades. In an effort to gain a deeper understanding of the interactions between these systems and immunocompetent cells, we describe here a systematic and study on three types of polymeric nanocapsules (NCs). These carriers, which contained protamine (PR), polyarginine (PARG), or chitosan (CS) in the external shell, and their corresponding nanoemulsion were prepared, and their main physicochemical properties were characterized.

Synergistic Effect of Metal Oxide Nanoparticles on Cell Viability and Activation of MAP Kinases and NFκB.

In recent years, there has been an increase in the production of several types of nanoparticles (Nps) for different purposes. Several studies have been performed to analyse the toxicity induced by some of these individual Nps, but data are scarce on the potential hazards or beneficial effects induced by a range of nanomaterials in the same environment. The purpose of the study described here was to evaluate the toxicological effects induced by in vitro exposure of human cells to ZnO Nps in combination with different concentrations of other metal oxide Nps (Al₂O₃, CeO₂, TiO₂ and Y₂O₃).

Crystal structure dependent in vitro antioxidant activity of biocompatible calcium gallate MOFs.

Two novel 3-D coordination polymers, denoted MIL-155 and MIL-156 (MIL stands for Materials Institute Lavoisier), built up from calcium and the naturally occurring gallic acid (Hgal), have been hydrothermally synthesized and their crystal structures were determined by single-crystal X-ray diffraction. These solids are based on different inorganic subunits: infinite chains of edge-sharing dimers of CaO polyhedra linked through partially deprotonated gallate ligands (Hgal) for MIL-155 or [Ca(HO)(Hgal)]·2HO, and ribbon-like inorganic subunits containing both eight-fold or six-fold coordinated Ca ions linked through fully deprotonated gallate ligands (gal) for MIL-156 or [CaK(HO)(gal)]·nHO (n∼ 5). Both solids contain small channels filled with water molecules, with, however no accessible porosity towards N at 77 K.

Analysis of the activation routes induced by different metal oxide nanoparticles on human lung epithelial cells.

Nanoparticles (Nps) can induce toxicity in the lung by accidental or intentional exposure. The main objective of the study reported here was to characterize the effect that four metal oxide Nps (CeO, TiO, AlO and ZnO) had at the cellular level on a human lung epithelial cell line. This goal was achieved by studying the capacity of the Nps to activate the main mitogen-activated protein kinases (MAPKs) and the nuclear factor NFκB.

Metal oxide nanoparticles interact with immune cells and activate different cellular responses.

Besides cell death, nanoparticles (Nps) can induce other cellular responses such as inflammation. The potential immune response mediated by the exposure of human lymphoid cells to metal oxide Nps (moNps) was characterized using four different moNps (CeO, TiO, AlO, and ZnO) to study the three most relevant mitogen-activated protein kinase subfamilies and the nuclear factor kappa-light-chain-enhancer of the activated B-cell inhibitor, IκBα, as well as the expression of several genes by immune cells incubated with these Nps. The moNps activated different signaling pathways and altered the gene expression in human lymphocyte cells.

Antitumor activity and systemic effects of PVM/MA-shelled selol nanocapsules in lung adenocarcinoma-bearing mice.

Selol is a semi-synthetic compound containing selenite that is effective against cancerous cells and safer for clinical applications in comparison with other inorganic forms of selenite. Recently, we have developed a formulation of poly(methyl vinyl ether-co-maleic anhydride)-shelled selol nanocapsules (SPN), which reduced the proliferative activity of lung adenocarcinoma cells and presented little deleterious effects on normal cells in in vitro studies. In this study, we report on the antitumor activity and systemic effects induced by this formulation in chemically induced lung adenocarcinoma-bearing mice.

Stealth monoolein-based nanocarriers for delivery of siRNA to cancer cells.

Unlabelled: While the delivery of small interfering RNAs (siRNAs) is an attractive strategy to treat several clinical conditions, siRNA-nanocarriers' stability after intravenous administration is still a major obstacle for the development of RNA-interference based therapies. But, although the need for stability is well recognized, the notion that strong stabilization can decrease nanocarriers' efficiency is sometimes neglected. In this work we evaluated two stealth functionalization strategies to stabilize the previously validated dioctadecyldimethylammonium bromide (DODAB):monoolein (MO) siRNA-lipoplexes.

A quantitative binding study of fibrinogen and human serum albumin to metal oxide nanoparticles by surface plasmon resonance.

The interaction of plasma proteins with metal oxide nanoparticles (NPs) is important due to the potential biomedical application of these NPs. In this study, new approaches were applied to measure quantitatively the kinetics and affinities of fibrinogen and human serum albumin (HSA) for TiO2, CeO2, Al2O3 and ZnO NPs immobilized on a sensor chip. Real-time surface plasmon resonance (SPR) measurements showed that fibrinogen interacted with TiO2 and CeO2 NPs with high affinity (135 and 40 pM, respectively) and to Al2O3 NPs with moderate affinity (15 nM).

Heparin-engineered mesoporous iron metal-organic framework nanoparticles: toward stealth drug nanocarriers.

The specific modification of the outer surface of the promising porous metal-organic framework nanocarriers (nanoMOFs) preserving their characteristic porosity is still a major challenge. Here a simple, fast, and biofriendly method for the external functionalization of the benchmarked mesoporous iron(III) trimesate nanoparticles MIL-100(Fe) with heparin, a biopolymer associated with longer-blood circulation times is reported. First, the coated nanoparticles showed intact crystalline structure and porosity with improved colloidal stability under simulated physiological conditions, preserving in addition its encapsulation and controlled release capacities.