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.

The development and use of mitochondria-targeted photosensitizers (PSs) hold great promise for enhancing the therapeutic efficacy and minimizing the side effects of photodynamic therapy (PDT). Although many studies have shown that coupling lipophilic cations to PSs facilitates their targeting to mitochondria, this process leads to a nonspecific distribution of PSs in the body and undesired systemic toxicity. Herein, three boron dipyrromethene (BODIPY) PSs conjugated with pyridine cations (1Py-BDP, 2Py-BDP, and 3Py-BDP) were synthesized to systematically evaluate the effects of the cationic pyridine number on the cytotoxicity and mitochondria-targeting property of the PSs for precise cancer PDT. To increase their stability in biological systems, these BODIPY PSs were encapsulated with an amphiphilic polymer (DSPE-mPEG2000) to afford PS-loaded liposomal nanoparticles designated 1Py-BDP@Lipos, 2Py-BDP@Lipos, and 3Py-BDP@Lipos. The results demonstrated that 2Py-BDP@Lipos showed higher efficiency for targeted delivery of the PSs to mitochondria compared with 1Py-BDP@Lipos and 3Py-BDP@Lipos. Moreover, the cytotoxicity of these BODIPY PSs was enhanced with the increase in the number of pyridine cations. In vivo results confirmed that liposomal encapsulation enhanced the tumor accumulation and retention of 2Py-BDP, which could effectively inhibit tumor growth under 660 nm laser irradiation. This study demonstrates that the conjugation of two pyridine cations with BODIPY PSs leads to improved targeting to mitochondria while maintaining low toxicity, thus facilitating the design of mitochondria-targeted PSs for in vivo PDT applications.

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.

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.