Integration of Antimicrobials and Delivery Systems: Synergistic Antibiofilm Activity with Biodegradable Nanoemulsions Incorporating Pseudopyronine Analogs

Multi-drug-resistant (MDR) bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), pose a significant challenge in healthcare settings. Small molecule antimicrobials (SMAs) such as α-pyrones have shown promise as alternative treatments for MDR infections. However, the hydrophobic nature of many SMAs limits their solubility and efficacy in complex biological environments. In this study, we encapsulated pseudopyronine analogs (PAs) in biodegradable polymer nanoemulsions (BNEs) for efficient eradication of biofilms. We evaluated a series of PAs with varied alkyl chain lengths and examined their antimicrobial activity against Gram-positive pathogens (S. aureus, MRSA, and B. subtilis). The selected PA with the most potent antibiofilm activity was incorporated into BNEs for enhanced solubility and penetration into the EPS matrix (PA-BNEs). The antimicrobial efficacy of PA-BNEs was assessed against biofilms of Gram-positive strains. The BNEs facilitated the solubilization and effective delivery of the PA deep into the biofilm matrix, addressing the limitations of hydrophobic SMAs. Our findings demonstrated that the PA2 exhibited synergistic antibiofilm activity when it was loaded into nanoemulsions. This study presents a promising platform for addressing MDR infections by combining pseudopyronine analogs with antimicrobial biodegradable nanoemulsions, overcoming challenges associated with treating biofilm infections

Novel hybrid organic/inorganic 2D quasiperiodic PC: from diffraction pattern to vertical light extraction

Recently, important efforts have been dedicated to the realization of a fascinating class of new photonic materials or metamaterials, known as photonic quasicrystals (PQCs), in which the lack of the translational symmetry is compensated by rotational symmetries not achievable by the conventional periodic crystals. As ever, more advanced functionality is demanded and one strategy is the introduction of non-linear and/or active functionality in photonic materials. In this view, core/shell nanorods (NRs) are a promising active material for light-emitting applications. In this article a two-dimensional (2D) hybrid a 2D octagonal PQC which consists of air rods in an organic/inorganic nanocomposite is proposed and experimentally demonstrated. The nanocomposite was prepared by incorporating CdSe/CdS core/shell NRs into a polymer matrix. The PQC was realized by electron beam lithography (EBL) technique. Scanning electron microscopy, far field diffraction and spectra measurements are used to characterize the experimental structure. The vertical extraction of the light, by the coupling of the modes guided by the PQC slab to the free radiation via Bragg scattering, consists of a narrow red emissions band at 690 nm with a full width at half-maximum (FWHM) of 21.5 nm. The original characteristics of hybrid materials based on polymers and colloidal NRs, able to combine the unique optical properties of the inorganic moiety with the processability of the host matrix, are extremely appealing in view of their technological impact on the development of new high performing optical devices such as organic light-emitting diodes, ultra-low threshold lasers, and non-linear devices

Identifying New Therapeutic Targets via Modulation of Protein Corona Formation by Engineered Nanoparticles

We introduce a promising methodology to identify new therapeutic targets in cancer. Proteins bind to nanoparticles to form a protein corona. We modulate this corona by using surface-engineered nanoparticles, and identify protein composition to provide insight into disease development.Using a family of structurally homologous nanoparticles we have investigated the changes in the protein corona around surface-functionalized gold nanoparticles (AuNPs) from normal and malignant ovarian cell lysates. Proteomics analysis using mass spectrometry identified hepatoma-derived growth factor (HDGF) that is found exclusively on positively charged AuNPs ((+)AuNPs) after incubation with the lysates. We confirmed expression of HDGF in various ovarian cancer cells and validated binding selectivity to (+)AuNPs by Western blot analysis. Silencing of HDGF by siRNA resulted s inhibition in proliferation of ovarian cancer cells.We investigated the modulation of protein corona around surface-functionalized gold nanoparticles as a promising approach to identify new therapeutic targets. The potential of our method for identifying therapeutic targets was demonstrated through silencing of HDGF by siRNA, which inhibited proliferation of ovarian cancer cells. This integrated proteomics, bioinformatics, and nanotechnology strategy demonstrates that protein corona identification can be used to discover novel therapeutic targets in cancer

Role of Ionic Strength in the Formation of Stable Supramolecular Nanoparticle–Protein Conjugates for Biosensing

Monolayer-protected gold nanoparticles (AuNPs) exhibit distinct physical and chemical properties depending on the nature of the ligand chemistry. A commonly employed NP monolayer comprises hydrophobic molecules linked to a shell of PEG and terminated with functional end group, which can be charged or neutral. Different layers of the ligand shell can also interact in different manners with proteins, expanding the range of possible applications of these inorganic nanoparticles. AuNP-fluorescent Green Fluorescent Protein (GFP) conjugates are gaining increasing attention in sensing applications. Experimentally, their stability is observed to be maintained at low ionic strength conditions, but not at physiologically relevant conditions of higher ionic strength, limiting their applications in the field of biosensors. While a significant amount of fundamental work has been done to quantify electrostatic interactions of colloidal nanoparticle at the nanoscale, a theoretical description of the ion distribution around AuNPs still remains relatively unexplored. We perform extensive atomistic simulations of two oppositely charged monolayer-protected AuNPs interacting with fluorescent supercharged GFPs co-engineered to have complementary charges. These simulations were run at different ionic strengths to disclose the role of the ionic environment on AuNP–GFP binding. The results highlight the capability of both AuNPs to intercalate ions and water molecules within the gold–sulfur inner shell and the different tendency of ligands to bend inward allowing the protein to bind not only with the terminal ligands but also the hydrophobic alkyl chains. Different binding stability is observed in the two investigated cases as a function of the ligand chemistry

Protein coronas suppress the hemolytic activity of hydrophilic and hydrophobic nanoparticles

The role of nanoparticle surface hydrophobicity on hemolytic properties is established in the absence and presence of plasma proteins. Significantly, the formation of a plasma protein corona on the NP surface protects red blood cells from both hydrophilic and hydrophobic NP-mediated hemolysis