NIR-II light activated photodynamic therapy with protein-capped gold nanoclusters

The use of near-infrared (NIR) light for photodynamic therapy (PDT) is a promising strategy to circumvent the limitations of current PDT, in which visible light with limited tissue penetration depth is usually used. In the present study, alkyl thiolated gold nanoclusters (AuNCs) were co-modified with human serum albumin (HSA) and catalase (CAT), and then employed as a multifunctional, optical, theranostic nano-agent. In the AuNC@HSA/CAT system, the AuNCs were able to produce singlet oxygen under excitation by a 1, 064-nm laser, which locates in the second NIR window (NIR-II), and featured much lower tissue absorption and scattering, enabling NIR-II-triggered PDT. The HSA coating greatly improved the physiological stability of the nanoparticles, which showed efficient tumor retention after intravenous injection, as revealed by detecting the AuNC fluorescence. Moreover, the presence of CAT in the nanoparticles triggered decomposition of tumor endogenous H₂O₂ to generate oxygen, thereby enhancing the efficacy of PDT by relieving tumor hypoxia. Compared with conventional PDT using visible light, NIR-II-triggered PDT exhibits remarkably increased tissue penetration. Thus, we developed a new type of photosensitizing nano-agent that simultaneously enables in vivo fluorescence imaging, tumor hypoxia relief, and NIR-II light-induced in vivo PDT in the treatment of cancer.