Cell Wall Destruction and Internal Cascade Synergistic Antifungal Strategy for Fungal Keratitis

Abstract

Fungal keratitis is one of the most common blindness-causing diseases, but clinical antifungal treatment remains a challenge. The fungal cell wall and biofilm matrix which severely confine the drug preparation are the critical obstructive factors to therapeutic effects. Herein, we report ethylenediaminetetraacetic acid (EDTA) modified AgCu2O nanoparticles (AgCuE NPs) to disrupt the cell wall and then eradicate C. albicans through the internal cascade synergistic effects of ion-released chemotherapy, chemodynamic therapy, photodynamic therapy, and mild photothermal therapy. AgCuE NPs exhibited excellent antifungal activity both in preventing biofilm formation and in destroying mature biofilms. Furthermore, AgCuE NP based gel formulations were topically applied to kill fungi, reduce inflammation, and promote wound healing, using optical coherence tomography and photoacoustic imaging to monitor nanogel retention and therapeutic effects on the infected murine cornea model. The AgCuE NP gel showed good biosafety and no obvious ophthalmic and systemic side effects. This study suggests that the AgCuE NP gel is an effective and safe antifungal strategy for fungal keratitis with a favorable prognosis and potential for clinical translation.

Photothermal Nanomaterials: A Powerful Light-to-Heat Converter

“…742 The existence of biofilms, which hinder the penetration of nanocarriers and reduce drug susceptibility, is one of the significant barriers for clinical trials. 667 Various strategies have been explored to enhance the penetration of drug carriers by introducing targeting membranes, changing the protecting ligands/coatings, and optimizing the size and shape of the carriers. 743−747 Both biodegradability and biocompatibility can be achieved through integration with organic polymers.…”

“…Since silica-cored Au nanoshells served as the first photothermal nanomaterials for clinical use, more and more inorganic agents with strong absorption in the NIR region, high chemical stability, adjustable water solubility, and minimal cytotoxicity have entered clinical trials. , Clinical trials have also been underway for small organic molecules due to their good biodegradability, good repeatability, and simple preparation. , Nevertheless, the major challenges for the clinical implementation of photothermal nanomaterials are the complex metabolism and excretion behaviors . The representative works on PTT with diverse photothermal nanomaterials in recent years − are summarized in Table .…”

“…The tumor growth is efficiently curbed with the inhibition rate of 97% and eliminated with no recurrence for 30 days. As a result, PTT and its combinational therapies with demonstrated efficacy have been well developed as promising treatment options for various life-threatening diseases. ,,− …”

Ethosomal Nanoformulations for Combinational Photothermal Therapy of Fungal Keratitis

“…Recently, AgCuO 2 nanoparticles modified with EDTA were reported for a synergistic photothermal, photodynamic, chemotherapy, and chemodynamic therapy to overcome multi‐drug resistant fungal keratitis. [ 41 ] Another study reported the development of modified hypocrellin using organic cages for combinational photodynamic therapy against multidrug resistant Candida spp. [ 42 ] However, biocompatibility and biodegradability of the nanocarrier is an important prerequisite to potentially qualify into the clinics.…”

Hybrid Biomimetic Membrane Coated Particles-Mediated Bacterial Ferroptosis for Acute MRSA Pneumonia

“…The integrity of the bacterial envelope can maintain the vitality, virulence, and normal functional morphology of the bacteria. , More importantly, the lipid in the membrane bilayer is the key buffer of reactive oxygen species (ROS), which can balance the oxidation and reduction states of the bacteria . A special form of death caused by iron-dependent lipid peroxidation is defined as ferroptosis .…”