NIR-II responsive multi-functional scaffold with PTT/CDT/CT/MHT and ion synergistic effects for all-in-one treatment of osteosarcoma-associated bone defects

Abstract

In terms of treating osteosarcoma, severe challenges are often encountered, such as the easy metastasis and recurrence of residual tumor cells after surgery, as well as the difficulty of self-repair of bone defects. Here, we developed MgFe-layered double hydroxides (MgFe-LDHs) to load anti-tumor drug curcumin (Cur), and further utilized them to surface modify 3D printed PLLA scaffold to construct a NIR-II responsive scaffold (PD-Fe-LDHs@Cur), which can meet the dual needs of anti-tumor and bone repair, thereby achieving the all-in-one treatment goal of osteosarcoma-associated bone defects. First, the scaffold triggers PTT, CDT, and CT effects simultaneously under NIR-II light and tumor microenvironment to kill tumor cells. Notably, the PTT effect can accelerate the release of Fe³⁺ and Cur, which is beneficial for improving the efficiency of CDT and CT effects, thus better exerting the synergistic anti-tumor effects of PTT, CDT, and CT. Subsequently, the scaffold can further exert MHT effect to synergistically stimulate angiogenesis and osteogenic differentiation with ionic effect and alkaline microenvironment generated by MgFe-LDHs degradation, thereby promoting bone regeneration more effectively. This multi-effect combined scaffold possesses excellent anti-tumor, angiogenic, and osteogenic activities, as well as the advantages of simple operation and low cost, thus exhibiting great potential for treating osteosarcoma-associated bone defects.