NO-driven self-propelled nanomotors with deep biofilm penetration for synergistic therapy of peri-implantitis.

Phototherapy as an adjuvant treatment for peri-implantitis (PI) still faces multiple challenges in clinical translation, including weak targeting capability of photosensitizers, poor biofilm penetration, and lack of immunomodulatory and osteogenic functions. To address these limitations, a core-shell nanomotor (IHPS) was constructed, whereby a hollow mesoporous polydopamine core encapsulating indocyanine green (ICG) was coated with S-nitrosothiol-modified ε-polylysine. Under near-infrared light excitation, the IHPS utilizes the positive surface charge provided by ε-polylysine to actively target plaque biofilms, and employs the photothermal effect of ICG to trigger burst release of nitric oxide (NO), thereby enhancing its penetration capacity into the deep regions of the biofilm through a self-propelled mechanism. The released NO can react with reactive oxygen species generated by ICG-mediated photodynamic therapy to form peroxynitrite, further synergistically improving antibacterial and biofilm eradication efficacy. Moreover, under physiological conditions, the IHPS enables sustained and slow release of NO, effectively promoting macrophage polarization toward the M2 phenotype to suppress inflammation, and enhancing osteogenic differentiation via activation of the sGC-cGMP-PKG signaling pathway. Ultimately, this approach achieves synergistic antibacterial, immunomodulatory, and bone regeneration effects at the infection site. This study provides a novel multifunctional therapeutic strategy with promising clinical translation potential for the treatment of PI.