Dendronized Ag/Au Nanomats: Antimicrobial Scaffold for Wound Healing Bandages.

Electrospun polymer nanofibers, due to high surface area-to-volume ratio, high porosity, good mechanical strength, and ease of functionalization, appear as promising multifunctional materials for biomedical applications. Thanks to their unidirectional structure, imitating the extracellular matrix (ECM), they can be used as scaffolds for cell adhesion and proliferation. In addition, the incorporation of active groups inside nanofiber can give properties for bactericides. The proposed nanomats incorporate nanoparticles templated within the electrospun nanofibers that prevent infections and stimulate tissue regeneration. The generated hybrid electrospun nanofibers are composed of a copolymer of L-lactide-block-ε-caprolactone (PL-b-CL), 70:30, blended with homopolymer polyvinylpyrrolidone (PVP) and gold (Au) nanoparticles. A low cytotoxicity and slightly increased immunoreactivity, stimulated by the nanomat, are observed. Moreover, the decoration of the hybrid nanomat with dendronized silver nanoparticles (Dend-Ag) improves their antibacterial activity against antibiotic-resistant Pseudomonas aeruginosa. The use of Dend-Ag for decorating offers several functional effects; namely, it enhances the antibacterial properties of the produced nanomats and induces a significant increase within macrophages' cytotoxicity. The unidirectional nanostructures of the generated hybrid nanomats demonstrate unique collective physio-chemical and biological properties suitable for a wide range of biomedical applications. Here, the antibacterial properties facilitate an optimal environment, contributing to accelerated wound healing.

Dendritic systems for bacterial outer membrane disruption as a method of overcoming bacterial multidrug resistance.

The alarming rise of multi-drug resistant microorganisms has increased the need for new approaches through the development of innovative agents that are capable of attaching to the outer layers of bacteria and causing permanent damage by penetrating the bacterial outer membrane. The permeability (disruption) of the outer membrane of Gram-negative bacteria is now considered to be one of the main ways to overcome multidrug resistance in bacteria. Natural and synthetic permeabilizers such as AMPs and dendritic systems seem promising. However, due to their advantages in terms of biocompatibility, antimicrobial capacity, and wide possibilities for modification and synthesis, highly branched polymers and dendritic systems have gained much more interest in recent years. Various forms of arrangement, and structure of the skeleton, give dendritic systems versatile applications, especially the possibility of attaching other ligands to their surface. This review will focus on the mechanisms used by different types of dendritic polymers, and their complexes with macromolecules to enhance their antimicrobial effect, and to permeabilize the bacterial outer membrane. In addition, future challenges and potential prospects are illustrated in the hope of accelerating the advancement of nanomedicine in the fight against resistant pathogens.

Overview of mechanism and consequences of endothelial leakiness caused by metal and polymeric nanoparticles.

Nanoparticles (NPs) exhibit unique physicochemical properties that enable them to overcome biological barriers and to be considered one of the best materials with anticancer properties. Most of the administered NPs that end up in the bloodstream interact with the endothelial layer. The interaction of the NPs with the endothelium widens the existing gaps or induces new ones in the monolayer of vascular endothelial cells, thus increasing the access to the target sites in the organism. This type of interaction can lead to NP-modulated endothelial leakiness (NanoEL). The most important factors determining NanoEL are the physicochemical properties of the NPs. NP-modulated endothelial leakiness can lead to the discovery of new therapeutic targets and strategies to improve drug delivery through controlling and regulating NanoEL. Nevertheless, the NanoEL mechanism also carries some limitations that result from an incomplete understanding of NP metabolism and toxicity, and the possibility of their participation in the unintended bidirectional vascular permeability, which may contribute to the formation of cancer metastases. In this review we are focusing on the effect of metal and polymeric NPs on mechanism and degree of induction of NanoEL, as well as on the benefits and risks of using NPs that induce endothelial leakiness.

Hybrid Nanomat: Copolymer Template CdSe Quantum Dots In Situ Stabilized and Immobilized within Nanofiber Matrix.

Fabrication and characterization of hybrid nanomats containing quantum dots can play a prominent role in the development of advanced biosensors and bio-based semiconductors. Owing to their size-dependent properties and controlled nanostructures, quantum dots (QDs) exhibit distinct optical and electronic characteristics. However, QDs include heavy metals and often require stabilizing agents which are toxic for biological applications. Here, to mitigate the use of toxic ligands, cadmium selenide quantum dots (CdSe QDs) were synthesized in situ with polyvinylpyrrolidone (PVP) at room temperature. The addition of PVP polymer provided size regulation, stability, and control over size distribution of CdSe QDs. The characterization of the optical properties of the CdSe QDs was performed using fluorescence and ultraviolet-visible (UV-Vis) spectroscopy. CdSe QDs exhibited a typical absorbance peak at 280 nm and a photoluminescence emission peak at 580 nm. Transmission electron microscopy (TEM) micrographs demonstrated that CdSe QDs having an average size of 6 ± 4 nm were obtained via wet chemistry method. CdSe QDs were immobilized in a blend of PVP and poly(L-lactide-co-ε-caprolactone) (PL-b-CL) copolymer that was electrospun to produce nanofibers. Scanning electron microscopy (SEM), thermal analyses and attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR) were used to characterize properties of fabricated nanofibers. Both pristine and hybrid nanofibers possessed cylindrical geometry and rough surface features, facilitating increased surface area. Infrared absorption spectra showed a slight shift in absorbance peaks due to interaction of PVP-coated CdSe QDs and nanofiber matrix. The presence of CdSe QDs influenced the fiber diameter and their thermal stability. Further, in vitro biological analyses of hybrid nanofibers showed promising antibacterial effect and decline in cancer cell viability. This study offers a simple approach to obtain hybrid nanomats immobilized with size-controlled PVP-coated CdSe QDs, which have potential applications as biosensors and antibacterial and anticancer cell agents.

The effect of surface modification of dendronized gold nanoparticles on activation and release of pyroptosis-inducing pro-inflammatory cytokines in presence of bacterial lipopolysaccharide in monocytes.

Biomedical applications of gold nanoparticles (AuNPs) may be limited by their toxicological effects. Although surface-modified AuNPs can induce apoptosis, less is known about whether they can induce other types of cell death. Pyroptosis, an inflammatory type of programmed cell death, can be induced in immune cells, especially macrophages, by bacterial endotoxins. Therefore, in this study, dendronized AuNPs were combined with bacterial lipopolysaccharides (LPSs) as the main stimulators of pro-inflammatory responses to test the induction of pyroptosis in THP-1 myeloid cell line. These AuNPs induced caspase-1 activity (3-4 times more compared to control) and enhanced the release of interleukin (IL)-18 and IL-1ß without inducing gasdermin D cleavage and related pore formation. The production of pro-inflammatory cytokines occurred mainly visible during LPS treatment, although their secretion was observed only after administration of dendronized AuNPs (release of IL-1ß to supernatant up to 80 pg/mL). These findings suggest that dendronized AuNPs can induce pyroptosis-like inflammatory mechanisms and that these mechanisms are enhanced in the presence of bacterial LPS. The intensity of this effect was dependent on AuNP surface modification. These results shed new light on the cytotoxicity of metal NPs, including immune responses, indicating that surface modifications play crucial roles in their nanotoxicological effects.