RESUMO
Chronic wounds containing opportunistic bacterial pathogens are a growing problem, as they are the primary cause of morbidity and mortality in developing and developed nations. Bacteria can adhere to almost every surface, forming architecturally complex communities called biofilms that are tolerant to an individual's immune response and traditional treatments. Wound dressings are a primary source and potential treatment avenue for biofilm infections, and research has recently focused on using nanoparticles with antimicrobial activity for infection control. This Review categorizes nanoparticle-based approaches into four main types, each leveraging unique mechanisms against biofilms. Metallic nanoparticles, such as silver and copper, show promising data due to their ability to disrupt bacterial cell membranes and induce oxidative stress, although their effectiveness can vary based on particle size and composition. Phototherapy-based nanoparticles, utilizing either photodynamic or photothermal therapy, offer targeted microbial destruction by generating reactive oxygen species or localized heat, respectively. However, their efficacy depends on the presence of light and oxygen, potentially limiting their use in deeper or more shielded biofilms. Nanoparticles designed to disrupt extracellular polymeric substances directly target the biofilm structure, enhancing the penetration and efficacy of antimicrobial agents. Lastly, nanoparticles that induce biofilm dispersion represent a novel strategy, aiming to weaken the biofilm's defense and restore susceptibility to antimicrobials. While each method has its advantages, the selection of an appropriate nanoparticle-based treatment depends on the specific requirements of the wound environment and the type of biofilm involved. The integration of these nanoparticles into wound dressings not only promises enhanced treatment outcomes but also offers a reduction in the overall use of antibiotics, aligning with the urgent need for innovative solutions in the fight against antibiotic-tolerant infections. The overarching objective of employing these diverse nanoparticle strategies is to replace antibiotics or substantially reduce their required dosages, providing promising avenues for biofilm infection management.
RESUMO
Hypoxia in solid tumors, including head and neck cancer (HNC), contributes to treatment resistance, aggressive phenotypes, and poor clinical outcomes. Perfluorocarbon nanodroplets have emerged as promising oxygen carriers to alleviate tumor hypoxia. However, a thorough characterization of the hypoxia alleviation effects in terms of sustenance of oxygenated environments have not been thoroughly studied. In this study, we developed and characterized perfluoropentane nanodroplets (PFP NDs) for co-delivery of oxygen and the photoactivatable drug or photosensitizer benzoporphyrin derivative (BPD) to hypoxic HNC spheroids. The PFP NDs exhibited excellent stability, efficient oxygen loading/release, and biocompatibility. Using 3D multicellular tumor spheroids of FaDu and SCC9 HNC cells, we demonstrated the ability of oxygenated PFP NDs to penetrate the hypoxic core and alleviate hypoxia, as evidenced by reduced fluorescence of a hypoxia-sensing reagent and downregulation of hypoxia-inducible factors HIF-1α and HIF-2α. BPD-loaded PFP NDs successfully delivered the photosensitizer into the spheroid core in a time-dependent manner. These findings highlight the potential of PFP NDs as a co-delivery platform to overcome hypoxia-mediated treatment resistance and improve therapy outcomes in HNC.