Synergistic Photodynamic/Antibiotic Therapy with Photosensitive MOF-Based Nanoparticles to Eradicate Bacterial Biofilms.

Bacterial biofilms pose a serious threat to human health, as they prevent the penetration of antimicrobial agents. Developing nanocarriers that can simultaneously permeate biofilms and deliver antibacterial agents is an attractive means of treating bacterial biofilm infections. Herein, photosensitive metal-organic framework (MOF) nanoparticles were developed to promote the penetration of antibiotics into biofilms, thereby achieving the goal of eradicating bacterial biofilms through synergistic photodynamic and antibiotic therapy. First, a ligand containing benzoselenadiazole was synthesized and incorporated into MOF skeletons to construct benzoselenadiazole-doped MOFs (Se-MOFs). The growth of the Se-MOFs could be regulated to obtain nanoparticles (Se-NPs) in the presence of benzoic acid. The singlet oxygen (1O2) generation efficiencies of the Se-MOFs and Se-NPs were evaluated. The results show that the Se-NPs exhibited a higher 1O2 generation efficacy than the Se-MOF under visible-light irradiation because the small size of the Se-NPs was conducive to the diffusion of 1O2. Afterward, an antibiotic drug, polymyxin B (PMB), was conjugated onto the surface of the Se-NPs via amidation to yield PMB-modified Se-NPs (PMB-Se-NPs). PMB-Se-NPs exhibit a synergistic antibacterial effect by specifically targeting the lipopolysaccharides present in the outer membranes of Gram-negative bacteria through surface-modified PMB. Benefiting from the synergistic therapeutic effects of antibiotic and photodynamic therapy, PMB-Se-NPs can efficiently eradicate bacterial biofilms at relatively low antibiotic doses and light intensities, providing a promising nanocomposite for combating biofilm infections.

Photodynamic Inactivation of Bacteria and Biofilms with Benzoselenadiazole-Doped Metal-Organic Frameworks.

Bacterial biofilms are difficult to treat due to their resistance to traditional antibiotics. Although photodynamic therapy (PDT) has made significant progress in biomedical applications, most photosensitizers have poor water solubility and can thus aggregate in hydrophilic environments, leading to the quenching of photosensitizing activity in PDT. Herein, a benzoselenadiazole-containing ligand was designed and synthesized to construct the zirconium (IV)-based benzoselenadiazole-doped metal-organic framework (Se-MOF). Characterizations revealed that Se-MOF is a type of UiO-68 topological framework with regular crystallinity and high porosity. Compared to the MOF without benzoselenadiazole, Se-MOF exhibited a higher 1O2 generation efficacy and could effectively kill Staphylococcus aureus bacteria under visible-light irradiation. Importantly, in vitro biofilm experiments confirmed that Se-MOF could efficiently inhibit the formation of bacteria biofilms upon visible-light exposure. This study provides a promising strategy for developing MOF-based PDT agents, facilitating their transformation into clinical photodynamic antibacterial applications.

Highly Effective Generation of Singlet Oxygen by an Imidazole-Linked Robust Photosensitizing Covalent Organic Framework.

Developing effective photosensitizers to initiate the generation of singlet oxygen (1O2) is of great significance in both chemistry and physiology. Herein, linking the photoactive porphyrin moieties by in situ-formed robust imidazole groups, a covalent organic framework (COF), PyPor-COF, was successfully designed and synthesized. Detailed characterizations reveal that it not only possesses high crystallinity, permanent porosity, and robust stability but also shows a semiconductive photoresponse activity. As demonstrated by electron paramagnetic resonance experiments, the COF can initiate the generation of 1O2 efficiently under visible-light irradiation, the efficiency of which is higher than that of the pristine porphyrin-based reactant and even higher than some commonly used commercially available photosensitizing agents. Anticancer experiments prove that it can efficiently trigger the production of 1O2 in a physiological environment. This work demonstrates that the imidazole-linked porphyrin-incorporated COF is a highly promising photosensitizer that can even be applied in photodynamic therapy.