Professor Chung-Ang University Anseong-si, Kyonggi-do, Republic of Korea
Introduction:: Bacterial infections pose a significant threat to human health, and antibiotic resistance has become a major challenge in treating these infections. Furthermore, the emergence of multidrug-resistant (MDR) bacteria has limited the effectiveness of antibiotics. Photodynamic therapy (PDT) has been used to treat bacterial infections with several advantages over traditional antibiotics including low toxicity, repeatability, and minimal invasiveness. Despite the promising potential of PDT, the low penetration of the external light sources is limited. Chemodynamic therapy (CDT) has emerged to be reactive oxygen species-based therapeutic modality. CDT utilizes endogenous H2O2 to produce hydroxyl radicals (·OH) via Fenton or Fenton-like reactions. However, single therapeutic approach of CDT is not enough to control bacterial infections. Therefore, the combined multimodal approaches have been suggested to treat bacterial infections.
In this study, we newly designed Co2+-doped L-012 and chlorin e6-loaded CaCO3 (Co@CaCO3/L-012/Ce6 particles) for synergistically enhancing therapeutic effects on bacterial infections using the combined self-PDT and CDT approaches.
Materials and Methods:: In this study, we synthesize a Co@CaCO3/L-012/Ce6 particles for self-PDT and CDT approaches to control bacterial infections. The prepared particles were characterized with UV/Vis spectrophotometer and fluorescence spectrometer. Also, their particle structures and morphologies were analysed by Fourier transform-infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and field-emission scanning electron microscopy (FE-SEM). Chemiluminescence (CL) emission as light source from the particles under an inflammation environment was imaged using a small animal imaging system. Singlet oxygen and hydroxyl radicals for self-PDT and CDT were examined using the indicators such as 9,10-Anthracenediyl-bis(methylene)dimalonic acid (ABDA) and methylene blue. Antibacterial effects of particles were examined against gram negative and positive bacteria by performing Live and Dead staining, growth inhibition, and changes of morphology with FE-SEM.
Results, Conclusions, and Discussions:: The Co@CaCO3/L-012/Ce6 particles had the vaterite form and the particle sizes were ranged from 4 to 20 μm. The Co@CaCO3/L-012/Ce6 particles emitted the strong CL emission under an inflammatory environment. In addition, the particles could generate highly cytotoxic singlet oxygen without external light source and hydroxyl radicals under an inflammatory environment. More importantly, Co@CaCO3/L-012/Ce6 particles could effectively induce apoptosis of both gram-negative and -positive bacteria. Therefore, we believe that the prepared Co@CaCO3/L-012/Ce6 particles will be promising for the treatment of bacterial infections.