Bone-targeted ICG/Cyt c@ZZF-8 nanoparticles based on the zeolitic imidazolate framework-8: a new synergistic photodynamic and protein therapy for bone metastasis

Bone metastasis (BM) is a solid tumor confined to narrow bone marrow cavities with a relatively poor blood supply and hypoxic environment, making conventional anticancer treatments difficult. In our study, we fabricated nanoparticles (NPs) based on zeolitic imidazolate framework-8 (ZIF-8) loaded with indocyanine green (ICG, a photodynamic agent) and cytochrome c (Cyt c, an anticancer protein) with a surface modified by zoledronate (ZOL, a bone-targeting moiety) and a polyvinyl pyrrolidone (PVP) coating to increase their stability. The ICG/Cyt c@ZZF-8 NPs were expected to have synergistic antitumor therapy and bone protection efficiency. The in vitro and in vivo experiments showed the bone-targeted and pH-sensitive ability of ICG/Cyt c@ZZF-8 NPs, which could be engulfed by tumor cells and release the cargos. Upon 780 nm laser irradiation, ICG produces cytotoxic reactive oxygen species (ROS, ¹O₂) that directly kill tumor cells, and Cyt c with catalase-like activity can induce programmed cell death and decompose H₂O₂ to O₂, thus enhancing the PDT efficiency. The ZOL can further inhibit bone resorption. The ICG/Cyt c@ZZF-8 NPs showed improved antitumor and bone protection efficiency in a mouse model of BM. This study demonstrated a potential mode for the synergetic therapy of orthopedic diseases.