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Multifunctional self-oxygenating UCNP–chlorin e6–cyanobacteria nanoplatform: NIR-triggered photodynamic and photothermal therapy with efficacy against periodontitis-related bacteria

Shimeng Wang,Wenyue Sun,Rui Sun,Jiawei Li,Jiheng Cui,Jiahang Wei,Haipeng Liu,Biao Dong

Antibacterial photodynamic therapy (aPDT) exhibits promise in bacterial infection models. However, its effectiveness is often limited in scenarios of bacterial infection within hypoxic environments such as deep periodontal pockets. The present study aims to develop a method to increase the efficacy of aPDT by combining rare earth upconversion nanoparticles (UCNPs) with cyanobacteria, forming cyanobacterial oxygen photosynthesis nanoplatform. In addition, due to the non-photochemical quenching (NPQ) mechanism in algae, cyanobacteria convert excess light energy into thermal energy to achieve synergistic aPDT/photothermal therapy (PTT) effects. Two types of UCNPs were loaded with cyanobacterial cells, including NaYF 4 :Yb 3+ ,0.2 mol%Tm 3+ with blue emission for triggering photosynthesis, and NaErF 4 :0.5 mol%Tm 3+ @NaYF 4 :20 mol%Yb 3+ with red emission for exciting the photosensitizer Chlorin e6 (Ce6). The resulting nanoplatform is referred to as Cyan@UCNPs/Ce6. Both the blue light required for oxygen photosynthesis and red light for aPDT are generated via absorption and upconversion of near-infrared (NIR) light, which can deeply penetrate the tissue. Notably, both in vitro and in vivo experiments demonstrate the remarkable biocompatibility and potent synergistic aPDT/PTT effects. Compared with non-NIR irradiation, the metabolic activities of two common periodontitis bacteria ( F.nucleatum , P.gingivalis ) decrease from 0.80±0.04 and 0.71±0.03 to 0.30±0.01 and 0.17±0.01, respectively ( p < 0.05). The findings of this study demonstrate that the developed Cyan@UCNPs/Ce6 nanoplatform is a promising strategy for photoresponsive synergistic aPDT/PTT in the treatment of periodontitis.