Photosensitizable ZIF-8 BioMOF for Stimuli-Responsive Antimicrobial Phototherapy

Resistant pathogens are increasingly posing a heightened risk to healthcare systems, leading to a growing concern due to the lack of effective antimicrobial treatments. This has prompted the adoption of antimicrobial photodynamic therapy (aPDT), which eradicates microorganisms by generating reactive oxygen species (ROS) through the utilization of a photosensitizer, photons, and molecular oxygen. However, a challenge arises from the inherent characteristics of photosensitizers, including photobleaching, aggregation, and self-quenching. Consequently, a strategy has been devised to adsorb or bind photosensitizers to diverse carriers to facilitate their delivery. Notably, metal-organic frameworks (MOFs) have emerged as a promising means of transporting photosensitizers, even though achieving uniform particle sizes through room-temperature synthesis remains a complex task. In this work, we have tackled the issue of heterogeneous particle size distribution in MOFs, achieving a particle size of 150 ± 50 nm. Subsequently, we harnessed Zeolite Imidazolate Framework 8 (ZIF-8), an excellent subclass of biocompatible MOF, to effectively load two distinct categories of photosensitizers, namely, Rose Bengal (RB) and porphyrin, using a simple, straightforward, and single-step process. Our findings indicate that the prepared RB@ZIF-8 complex generates a more substantial amount of reactive singlet oxygen species when subjected to photoirradiation (using green light-emitting diode (LED)) at low concentrations, in comparison with porphyrin@ZIF-8, as demonstrated in in vitro experiments. Additionally, we investigated the pH-responsive behavior of the complex to ascertain its implications under biological conditions. Correspondingly, the RB@ZIF-8 complex exhibited a more favorable IC₅₀ value against Escherichia coli compared to bare photosensitizers, ZIF-8 alone, and other photosensitizer-loaded ZIF-8 complexes. This underscores the potential of BioMOF as a promising strategy for combatting multidrug-resistant bacteria across a spectrum of infection scenarios, complemented by its responsiveness to stimuli.