Conformation Dependent Architectures of Assembled Antimicrobial Peptides with Enhanced Antimicrobial Ability.

Antimicrobial peptides (AMPs) are a developing class of natural and synthetic oligopeptides with host defense mechanisms against a broad spectrum of microorganisms. With in-depth research on the structural conformations of AMPs, synthesis or modification of peptides has shown great potential in effectively obtaining new therapeutic agents with improved physicochemical and biological properties. Notably, AMPs with self-assembled properties have gradually become a hot research topic for various biomedical applications. Compared to monomeric peptides, these peptides can exist in diverse forms (e.g., nanoparticles, nanorods, and nanofibers) and possess several advantages, such as high stability, good biocompatibility, and potent biological functions, after forming aggregates under specific conditions. In particular, the stability and antibacterial property of these AMPs can be modulated by rationally regulating the peptide sequences to promote self-assembly, leading to the reconstruction of molecular structure and spatial orientation while introducing some peptide fragments into the scaffolds. In this work, four self-assembled AMPs are developed, and the relationship between their chemical structures and antibacterial activity is explored extensively through different experiments. Importantly, the evaluation of antibacterial performance in both in vitro and in vivo studies has provided a general guide for using self-assembled AMPs in subsequent treatments for combating bacterial infections.

Rapid synthesis of bismuth-organic frameworks as selective antimicrobial materials against microbial biofilms.

Antibiotic resistance is a global public health threat, and urgent actions should be undertaken for developing alternative antimicrobial strategies and approaches. Notably, bismuth drugs exhibit potent antimicrobial effects on various pathogens and promising efficacy in tackling SARS-CoV-2 and related infections. As such, bismuth-based materials could precisely combat pathogenic bacteria and effectively treat the resultant infections and inflammatory diseases through a controlled release of Bi ions for targeted drug delivery. Currently, it is a great challenge to rapidly and massively manufacture bismuth-based particles, and yet there are no reports on effectively constructing such porous antimicrobial-loaded particles. Herein, we have developed two rapid approaches (i.e., ultrasound-assisted and agitation-free methods) to synthesizing bismuth-based materials with ellipsoid- (Ellipsoids) and rod-like (Rods) morphologies respectively, and fully characterized physicochemical properties. Rods with a porous structure were confirmed as bismuth metal-organic frameworks (Bi-MOF) and aligned with the crystalline structure of CAU-17. Importantly, the formation of Rods was a 'two-step' crystallization process of growing almond-flake-like units followed by stacking into the rod-like structure. The size of Bi-MOF was precisely controlled from micro-to nano-scales by varying concentrations of metal ions and their ratio to the ligand. Moreover, both Ellipsoids and Rods showed excellent biocompatibility with human gingival fibroblasts and potent antimicrobial effects on the Gram-negative oral pathogens including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum. Both Ellipsoids and Rods at 50 â€‹µg/mL could disrupt the bacterial membranes, and particularly eliminate P. gingivalis biofilms. This study demonstrates highly efficient and facile approaches to synthesizing bismuth-based particles. Our work could enrich the administration modalities of metallic drugs for promising antibiotic-free healthcare.

A glutathione-responsive silica-based nanosystem capped with in-situ polymerized cell-penetrating poly(disulfide)s for precisely modulating immuno-inflammatory responses.

HYPOTHESIS: Precise modulation of immuno-inflammatory response is crucial to control periodontal diseases and related systemic comorbidities. The present nanosystem with the controlled-release and cell-penetrating manner enhances the inflammation modulation effects of baicalein in human gingival epithelial cells (hGECs) for better oral healthcare. EXPERIMENTS: We constructed a red-emissive mesoporous silica nanoparticle-based nanosystem with cell-penetrating poly(disulfide) (CPD) capping, through a facile in-situ polymerization approach. It was featured with a glutathione-responsive manner and instant cellular internalization capacity for precisely delivering baicalein intracellularly. Laboratory experiments assessed whether and how the nanosystem per se with the delivered baicalein could modulate immuno-inflammatory responses in hGECs. FINDINGS: The in-situ polymerized CPD layer capped the nanoparticles and yet controlled the release of baicalein in a glutathione-responsive manner. The CPD coating could facilitate cellular internalization of the nanosystem via endocytosis and thiol-mediated approaches. Notably, the intracellularly released baicalein effectively downregulated the expression of pro-inflammatory cytokines through inhibiting the NF-κB signaling pathway. The nanosystem per se could modulate immuno-inflammatory responses by passivating the cellular response to interlukin-1ß. This study highlights that the as-synthesized nanosystem may serve as a novel multi-functional vehicle to modulate innate host response via targeting the NF-κB pathway for precision healthcare.

Highly selective detection of Pd2+ ion in aqueous solutions with rhodamine-based colorimetric and fluorescent chemosensors.

In this study, we report a new class of rhodamine-based fluorescent sensors for highly selective and sensitive detection of Pd2+ ions in aqueous medium. A rhodamine-based palladium sensor RPS and a coumarin-rhodamine Förster resonance energy transfer (FRET)-pair based palladium sensor FPS were synthesized with the designed podand ligand for Pd2+ ion recognition. They showed both colorimetric change and fluorometric change in the presence of Pd2+ ion due to the opening of their spirolactam rings. Both chemosensors are highly selective to Pd2+ over the other 24 different metal ions and they are selective to palladium species in +2 oxidation state, RPS showed a 70-fold fluorescent turn-on while FPS showed a 1.75-fold ratiometric change at I599/I470. Furthermore, RPS showed low cell cytotoxicity and it was successfully used to image Pd2+ in BEAS-2B lung epithelial cells. © 2019 Elsevier Science. All rights reserved.

Red-Emissive Guanylated Polyene-Functionalized Carbon Dots Arm Oral Epithelia against Invasive Fungal Infections.

Oral candidiasis as a highly prevalent and recurrent infection in medically compromised individuals is mainly caused by the opportunistic fungal pathogen Candida albicans. This epithelial infection, if not controlled effectively, can progress to life-threatening systemic conditions and complications. The efficacy of current frontline antifungals is limited due to their poor bioavailability and systemic toxicity. As such, an efficient intervention is essential for controlling disease progression and recurrence. Herein, a theranostic nanoplatform (CD-Gu+-AmB) was developed to track the penetration of antifungals and perturb the invasion of C. albicans at oral epithelial tissues, via decorating the homemade red-emissive carbon dots (CD) with positively charged guanidine groups (Gu+) followed by conjugation with antifungal polyene (amphotericin B, AmB) in a reacting site-controllable manner. The generated CD-Gu+-AmB favorably gathered within the Candida cells and exhibited potent antifungal effects in both planktonic and biofilm forms. It selectively accumulated in the nuclei of human oral keratinocytes and exhibited undetectable toxicity to the host cells. Moreover, we reported for the first time the penetration and exfoliation profiles of CD in a three-dimensional organotypic model of human oral epithelial tissues, demonstrating that the extra- and intracellular accumulation of CD-Gu+-AmB effectively resisted the invasion of C. albicans by forming a "shielding" layer throughout the entire tissue. This study establishes a multifunctional CD-based theranostic nanoplatform functioning as a traceable and topically applied antifungal to arm oral epithelia, thereby shedding light on early intervention of mucosal candidiasis for oral and general health.