ABSTRACT
Fungal pathogens cause over 6.5 million life-threatening systemic infections annually, with mortality rates ranging from 20 to 95%, even with medical intervention. The World Health Organization has recently emphasized the urgent need for new antifungal drugs. However, the range of effective antifungal agents remains limited and resistance is increasing. This Review explores the current landscape of fungal infections and antifungal drugs, focusing on synthetic polymeric nanomaterials like nanoparticles that enhance the physicochemical properties of existing drugs. Additionally, we examine intrinsically antifungal polymers that mimic naturally occurring peptides. Advances in polymer characterization and synthesis now allow precise design and screening for antifungal activity, biocompatibility, and drug interactions. These antifungal polymers represent a promising new class of drugs for combating fungal infections.
ABSTRACT
More than two million people worldwide are affected by life-threatening, invasive fungal infections annually. Candida species are the most common cause of nosocomial, invasive fungal infections and are associated with mortality rates above 40%. Despite the increasing incidence of drug-resistance, the development of novel antifungal formulations has been limited. Here we investigate the antifungal mode of action and therapeutic potential of positively charged, synthetic peptide mimics to combat Candida albicans infections. Our data indicates that these synthetic polymers cause endoplasmic reticulum stress and affect protein glycosylation, a mode of action distinct from currently approved antifungal drugs. The most promising polymer composition damaged the mannan layer of the cell wall, with additional membrane-disrupting activity. The synergistic combination of the polymer with caspofungin prevented infection of human epithelial cells in vitro, improved fungal clearance by human macrophages, and significantly increased host survival in a Galleria mellonella model of systemic candidiasis. Additionally, prolonged exposure of C. albicans to the synergistic combination of polymer and caspofungin did not lead to the evolution of tolerant strains in vitro. Together, this work highlights the enormous potential of these synthetic peptide mimics to be used as novel antifungal formulations as well as adjunctive antifungal therapy.
Subject(s)
Antifungal Agents , Candida albicans , Candidiasis , Caspofungin , Drug Synergism , Peptides , Candida albicans/drug effects , Antifungal Agents/pharmacology , Humans , Caspofungin/pharmacology , Animals , Candidiasis/drug therapy , Candidiasis/microbiology , Peptides/pharmacology , Peptides/chemistry , Macrophages/drug effects , Macrophages/microbiology , Endoplasmic Reticulum Stress/drug effects , Cell Wall/drug effects , Microbial Sensitivity Tests , Mannans/pharmacology , Mannans/chemistry , Moths/microbiology , Moths/drug effects , Epithelial Cells/drug effects , Epithelial Cells/microbiology , Polymers/pharmacology , Polymers/chemistryABSTRACT
The escalating demand for plastics has resulted in a surge of plastic waste worldwide, posing a monumental environmental challenge. To address this issue, a versatile photo-oxidative degradation method applicable to seven distinct polymer families is proposed, comprising poly(isobutyl vinyl ether) (PIBVE), poly(2,3-dihydrofuran) (PDHF), poly(vinyl acetate) (PVAc), poly(n-butyl acrylate) (PBA), poly(methyl acrylate) (PMA), poly(vinyl chloride) (PVC), poly(dimethyl acrylamide) (PDMA), poly(ethylene oxide) (PEO), poly(oligo(ethylene glycol) methyl ether acrylate) (PEGMEA), and even poly(methyl methacrylate) (PMMA). This method employs photo-mediated hydrogen atom transfer (HAT) followed by oxidation to promote polymer degradation. This reaction is carried out under aerobic condition in the presence of iron trichloride (FeCl3) as a photocatalyst in combination with low-intensity purple light irradiation. The process can degrade up to 97% of the polymer in less than 3 h. This degradation process can be easily controlled by switching the light off, which allows for precise modulation of the degradation rate, enhancing the effectiveness of the method. Overall, this method provides a sustainable method for degrading various polymer types with low energy input.
ABSTRACT
Solvent-free photopolymerization of vinyl monomers to produce high modulus materials with applications in 3D printing and photoswitchable materials is demonstrated. Polymerizable eutectic (PE) mixtures are prepared by simply heating and stirring various molar ratios of N-isopropylacrylamide (NIPAM), acrylamide (AAm) and 2-hydroxyethyl methacrylate (HEMA). The structural and thermal properties of the resulting mixtures are evaluated by 1D and 2D NMR spectroscopy as well as differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). UV photocuring kinetics of the PE mixtures is evaluated via in situ photo-DSC and photorheology measurements. The PE mixtures cure rapidly and display storage moduli that are orders of magnitude greater than equivalent copolymers cured in an aqueous medium. The versatility of these PE systems is demonstrated through the addition of a photoswitchable spiropyran acrylate monomer, as well as applying the PE formulation as a stereolithography (SLA)-based 3D printing resin. Due to the hydrogen-bonding network in PE systems, 3D printing of the eutectic resin is possible in the absence of crosslinkers. The addition of a RAFT agent to reduce average polymer chain length enables 3D printing of materials which retain their shape and can be dissolved on demand in appropriate solvents.
ABSTRACT
Triboelectric nanogenerators (TENGs) are sustainable energy resources for powering electronic devices from miniature to large-scale applications. However, their output performance and stability can deteriorate significantly when TENGs are exposed to moisture or humidity caused by the ambient environment or human physiological activities. This review provides an overview of the recent research advancements in enhancing the humidity resistance of TENGs. Various approaches have been reviewed including encapsulation techniques, surface modification of triboelectric materials to augment hydrophobicity or superhydrophobicity, the creation of fibrous architectures for effective moisture dissipation, leveraging water assistance for TENG performance enhancement, and other strategies like charge excitation. These research efforts contribute to the improvement of environmental adaptability and lead to expanded practical TENG applications both as energy harvesters and self-powered sensors. The efficacy of these strategies and future challenges are also discussed to facilitate the continued development of resilient TENGs in high humidity environments.
ABSTRACT
Only a small proportion of global plastic waste is recycled, of which most is mechanically recycled into lower quality materials. The alternative, chemical recycling, enables renewed production of pristine materials, but generally comes at a high energy cost, particularly for processes like pyrolysis. This review focuses on light-driven approaches for chemically recycling and upcycling plastic waste, with emphasis on reduced energy consumption and selective transformations not achievable with heat-driven methods. We focus on challenging to recycle backbone structures composed of mainly CâC bonds, which lack functional groups i.e., esters or amides, that facilitate chemical recycling e.g., by solvolysis. We discuss the use of light, either in conjunction with heat to drive depolymerization to monomers or via photocatalysis to transform polymers into valuable small molecules. The structural prerequisites for these approaches are outlined, highlighting their advantages as well as limitations. We conclude with an outlook, addressing key challenges, opportunities, and provide guidelines for future photocatalyst (PC) development.
ABSTRACT
Invasive fungal infections impose a substantial global health burden. They cause more than 1.5 million deaths annually and are insufficiently met by the currently approved antifungal drugs. Antifungal peptides are a promising alternative to existing antifungal drugs; however, they can be challenging to synthesize, and are often susceptible to proteases in vivo. Synthetic polymers which mimic the properties of natural antifungal peptides can circumvent these limitations. In this study, we developed a library of 29 amphiphilic polyacrylamides with different charged units, namely, amines, guanidinium, imidazole, and carboxylic acid groups, representative of the natural amino acids lysine, arginine, histidine, and glutamic acid. Ternary polymers incorporating primary ammonium (lysine-like) or imidazole (histidine-like) groups demonstrated superior activity against Candida albicans and biocompatibility with mammalian cells compared to the polymers containing the other charged groups. Furthermore, a combination of primary ammonium, imidazole, and guanidinium (arginine-like) within the same polymer outperformed the antifungal drug amphotericin B in terms of therapeutic index and exhibited fast C. albicans-killing activity. The most promising polymer compositions showed synergistic effects in combination with caspofungin and fluconazole against C. albicans and additionally demonstrated activity against other clinically relevant fungi. Collectively, these results indicate the strong potential of these easily producible polymers to be used as antifungals.