Mohammad Okkeh

Staphylococci are among the most frequent bacteria known to cause biofilm-related infections. Pathogenic biofilms represent a global healthcare challenge due to their high tolerance to antimicrobials. In this study, water soluble polyethylene glycol (PEG)-coated gold nanospheres (28 ppm) and nanostars (15 ppm) with electrostatically adsorbed photosensitizer (PS) Toluidine Blue O (TBO) ∼4 μM were successfully synthesized and characterized as PEG-GNPs@TBO and PEG-GNSs@TBO. Both nanoconjugates and the TBO 4 μM solution showed remarkable, if similar, antimicrobial photodynamic inactivation (aPDI) effects at 638 nm, inhibiting the formation of biofilms by two Staphylococcal strains: a clinical methicillin-resistant Staphylococcus aureus (MRSA) isolate and Staphylococcus epidermidis (S. epidermidis) RP62A. Alternatively in biofilm eradication treatments, the aPDI effects of PEG-GNSs@TBO were more effective and yielded a 75% and 50% reduction in viable count of MRSA and S. epidermidis RP62A preformed biofilms, respectively and when compared with untreated samples. This reduction in viable count was even greater than that obtained through aPDI treatment using a 40 μM TBO solution. Confocal laser microscopy (CLSM) and scanning electron microscope (SEM) images of PEG-GNSs@TBO's aPDI treatments revealed significant changes in the integrity and morphology of biofilms, with fewer colony masses. The generation of reactive oxygen species (ROS) upon PEG-GNSs@TBO's aPDI treatment was detected by CLSM using a specific ROS fluorescent probe, demonstrating bright fluorescence red spots across the surfaces of the treated biofilms. Our findings shine a light on the potential synergism between gold nanoparticles (AuNPs) and photosensitizers in developing novel nanoplatforms to target Staphylococcal biofilm related infections.

In 2017 the World Health Organization (WHO) announced a list of the 12 multidrug-resistant (MDR) families of bacteria that pose the greatest threat to human health, and recommended that new measures should be taken to promote the development of new therapies against these superbugs. Few antibiotics have been developed in the last two decades. Part of this slow progression can be attributed to the surge in the resistance acquired by bacteria, which is holding back pharma companies from taking the risk to invest in new antibiotic entities. With limited antibiotic options and an escalating bacterial resistance there is an urgent need to explore alternative ways of meeting this global challenge. The field of medical nanotechnology has emerged as an innovative and a powerful tool for treating some of the most complicated health conditions. Different inorganic nanomaterials including gold, silver, and others have showed potential antibacterial efficacies. Interestingly, gold nanoparticles (AuNPs) have gained specific attention, due to their biocompatibility, ease of surface functionalization, and their optical properties. In this review, we will focus on the latest research, done in the field of antibacterial gold nanoparticles; by discussing the mechanisms of action, antibacterial efficacies, and future implementations of these innovative antibacterial systems.

Nanotechnology is in the spotlight of therapeutic innovation, with numerous advantages for tumor visualization and eradication. The end goal of the therapeutic use of nanoparticles, however, remains distant due to the limitations of nanoparticles to target cancer tissue. The functionalization of nanosystem surfaces with biological ligands is a major strategy for directing the actions of nanomaterials specifically to tumor cells. Cancer formation and metastasis are accompanied by profound alterations in protein glycosylation. Hence, the detection and targeting of aberrant glycans are of great value in cancer diagnosis and therapy. In this review, we provide a brief update on recent progress targeting aberrant glycosylation by functionalizing nanoparticles with glycan-binding molecules (with a special focus on lectins and anti-glycan antibodies) to improve the efficacy of nanoparticles in cancer targeting, diagnosis, and therapy and outline the challenges and limitations in implementing this approach. We envision that the combination of nanotechnological strategies and cancer-associated glycan targeting could remodel the field of cancer diagnosis and therapy, including immunotherapy.