Nanoscale fluconazole-constructed metal-organic frameworks with smart drug release for eradication of Candida biofilms in vulvovaginitis infection.

Fungal infections associated with oral, gynecological, and skin ailments pose significant clinical challenges. The presence of biofilms often hampers the efficacy of conventional antifungal drugs owing to the complex microenvironment they create. In this study, the widely used antifungal medication fluconazole is utilized as a foundational component to be incorporated into zinc 2-methylimidazolate frameworks, resulting in the synthesis of nanoscale fluconazole-constructed metal-organic frameworks (F-ZIF).

Heme-Mimetic Photosensitizer with Iron-Targeting and Internalizing Properties for Enhancing PDT Activity and Promoting Infected Diabetic Wound Healing.

The management of multibacterial infections remains clinically challenging in the care and treatment of chronic diabetic wounds. Photodynamic therapy (PDT) offers a promising approach to addressing bacterial infections. However, the limited target specificity and internalization properties of traditional photosensitizers (PSs) toward Gram-negative bacteria pose significant challenges to their antibacterial efficacy.

Synergy between pH- and hypoxia-responsiveness in antibiotic-loaded micelles for eradicating mature, infectious biofilms.

Antibiotic-loaded PEG/PAE-based micelles are frequently considered for eradicating infectious biofilms. At physiological pH, PEG facilitates transport through blood. Near an acidic infection-site, PAE becomes protonated causing micellar targeting to a biofilm.

Self-targeting of zwitterion-based platforms for nano-antimicrobials and nanocarriers.

Self-targeting antimicrobial platforms have yielded new possibilities for the treatment of infectious biofilms. Self-targeting involves stealth transport through the blood circulation towards an infectious biofilm, where the antimicrobial platform penetrates and accumulates in a biofilm in response to a change in environmental conditions, such as local pH. In a final step, nano-antimicrobials need to be activated or the antimicrobial cargo of nanocarriers released.

A Guanosine-Quadruplex Hydrogel as Cascade Reaction Container Consuming Endogenous Glucose for Infected Wound Treatment-A Study in Diabetic Mice.

Diabetic foot ulcers infected with antibiotic-resistant bacteria form a severe complication of diabetes. Antimicrobial-loaded hydrogels are used as a dressing for infected wounds, but the ongoing rise in the number of antimicrobial-resistant infections necessitates new, nonantibiotic based designs. Here, a guanosine-quadruplex (G )-hydrogel composed of guanosine, 2-formylphenylboronic acid, and putrescine is designed and used as a cascade-reaction container.

Encapsulation of Photothermal Nanoparticles in Stealth and pH-Responsive Micelles for Eradication of Infectious Biofilms In Vitro and In Vivo.

Photothermal nanoparticles can be used for non-antibiotic-based eradication of infectious biofilms, but this may cause collateral damage to tissue surrounding an infection site. In order to prevent collateral tissue damage, we encapsulated photothermal polydopamine-nanoparticles (PDA-NPs) in mixed shell polymeric micelles, composed of stealth polyethylene glycol (PEG) and pH-sensitive poly(β-amino ester) (PAE). To achieve encapsulation, PDA-NPs were made hydrophobic by electrostatic binding of indocyanine green (ICG).

Coating of a Novel Antimicrobial Nanoparticle with a Macrophage Membrane for the Selective Entry into Infected Macrophages and Killing of Intracellular Staphylococci.

Internalization of by macrophages can inactivate bacterial killing mechanisms, allowing intracellular residence and dissemination of infection. Concurrently, these staphylococci can evade antibiotics that are frequently unable to pass mammalian cell membranes. A binary, amphiphilic conjugate composed of triclosan and ciprofloxacin is synthesized that self-assemble through micelle formation into antimicrobial nanoparticles (ANPs).

Self-targeting, zwitterionic micellar dispersants enhance antibiotic killing of infectious biofilms-An intravital imaging study in mice.

Extracellular polymeric substances (EPS) hold infectious biofilms together and limit antimicrobial penetration and clinical infection control. Here, we present zwitterionic micelles as a previously unexplored, synthetic self-targeting dispersant. First, a pH-responsive poly(ε-caprolactone)--poly(quaternary-amino-ester) was synthesized and self-assembled with poly(ethylene glycol)--poly(ε-caprolactone) to form zwitterionic, mixed-shell polymeric micelles (ZW-MSPMs).

Recent Advances and Future Prospects on Adaptive Biomaterials for Antimicrobial Applications.

Bacterial infection is becoming the biggest threat to human health. The scenario is partly due to the ineffectiveness of the conventional antibiotic treatments against the emergence of multidrug-resistant bacteria and partly due to the bacteria living in biofilms or cells. Adaptive biomaterials can change their physicochemical properties in the microenvironment of bacterial infection, thereby facilitating either their interactions with bacteria or drug release.

Nanotechnology-based antimicrobials and delivery systems for biofilm-infection control.

Bacterial-infections are mostly due to bacteria in an adhering, biofilm-mode of growth and not due to planktonically growing, suspended-bacteria. Biofilm-bacteria are much more recalcitrant to conventional antimicrobials than planktonic-bacteria due to (1) emergence of new properties of biofilm-bacteria that cannot be predicted on the basis of planktonic properties, (2) low penetration and accumulation of antimicrobials in a biofilm, (3) disabling of antimicrobials due to acidic and anaerobic conditions prevailing in a biofilm, and (4) enzymatic modification or inactivation of antimicrobials by biofilm inhabitants. In recent years, new nanotechnology-based antimicrobials have been designed to kill planktonic, antibiotic-resistant bacteria, but additional requirements rather than the mere killing of suspended bacteria must be met to combat biofilm-infections.

Antimicrobial synergy of monolaurin lipid nanocapsules with adsorbed antimicrobial peptides against Staphylococcus aureus biofilms in vitro is absent in vivo.

Bacterial infections are mostly due to bacteria in their biofilm-mode of growth, while penetrability of antimicrobials into infectious biofilms and increasing antibiotic resistance hamper infection treatment. In-vitro, monolaurin lipid nanocapsules (ML-LNCs) carrying adsorbed antimicrobial peptides (AMPs) displayed synergistic efficacy against planktonic Staphylococcus aureus, but it has not been demonstrated, neither in-vitro nor in-vivo, that such ML-LNCs penetrate into infectious S. aureus biofilms and maintain synergy with AMPs.

Nanocarriers with conjugated antimicrobials to eradicate pathogenic biofilms evaluated in murine in vivo and human ex vivo infection models.

Conventional antimicrobials are becoming increasingly ineffective for treating bacterial infection due to the emergence of multi-drug resistant (MDR) pathogens. In addition, the biofilm-mode-of-growth of infecting bacteria impedes antimicrobial penetration in biofilms. Here, we report on poly(ethylene)glycol-poly(β-amino esters) (PEG-PAE) micelles with conjugated antimicrobials, that can uniquely penetrate biofilms, target themselves to bacterial cell surfaces once inside the low-pH environment of a biofilm and release conjugated antimicrobials through degradation of their ester-linkage with PAE by bacterial lipases.

Photoswitchable Micelles for the Control of Singlet-Oxygen Generation in Photodynamic Therapies.

Inadvertent photosensitizer-activation and singlet-oxygen generation hampers clinical application of photodynamic therapies of superficial tumors or subcutaneous infections. Therefore, a reversible photoswitchable system was designed in micellar nanocarriers using ZnTPP as a photosensitizer and BDTE as a photoswitch. Singlet-oxygen generation upon irradiation didnot occur in closed-switch micelles with ZnTPP/BDTE feeding ratios >1:10.