NIR-II-activated supramolecular LDH nanoarchitecture integrated with 3D-printed bioactive glass for hypoxia-resistant photodynamic osteosarcoma therapy and bone regeneration
TL;DR
A novel functionalized 3D-printed scaffold with NIR-II responsiveness (BGS/I-LDH@MgO2), designed to simultaneously address the dual needs of inhibiting osteosarcoma recurrence and promoting bone regeneration, demonstrates excellent anti-tumor and osteogenic properties.
Abstract
The clinical management of osteosarcoma faces critical challenges, including postoperative recurrence and metastasis of residual tumor cells, chemotherapy resistance, and impaired self-repair capacity due to extensive bone defects following tumor resection. Herein, we develop a novel functionalized 3D-printed scaffold with NIR-II responsiveness (BGS/I-LDH@MgO2), designed to simultaneously address the dual needs of inhibiting osteosarcoma recurrence and promoting bone regeneration. This scaffold consists of 3D-printed bioactive glass scaffold (BGS) and MgO2-modified ZnAl-layered double hydroxides (ZnAl-LDHs) intercalated with 5-iodo-isophthalic acid (I-IPA). Under NIR-II irradiation, the scaffold effectively triggers a photodynamic therapy (PDT) effect to eliminate osteosarcoma cells. Notably, the incorporation of MgO2 enables oxygen release within the tumor microenvironment, alleviating hypoxia and enhancing PDT efficacy for superior antitumor performance. Furthermore, the degradation of ZnAl-LDHs and MgO2 releases Mg2+ and Zn2+ ions and generates a mildly alkaline microenvironment, which collectively facilitate the osteogenic differentiation of bone marrow mesenchymal stem cells and accelerate the process of bone healing. This functionalized 3D-printed scaffold demonstrates excellent anti-tumor and osteogenic properties, showing great promise for the treatment of osteosarcoma-associated bone defects.