Self-assembled injectable Icariin@ Ti3C2Tx/doxorubicin hydrogel preserving osteogenesis while synergizing photodynamic and chemodynamic therapy for osteosarcoma

Local therapy involving injectable hydrogel systems loaded with doxorubicin (DOX) has garnered significant attention in the realm of osteosarcoma (OS) research. Nevertheless, it has been noted that the local delivery of high-dose DOX exerts a pronounced inhibitory impact on osteogenesis, which is detrimental to the restoration of functional capabilities after OS treatment. To address this challenge, we have designed a self-assembled injectable hydrogel system that integrates photodynamic and chemodynamic therapy, aiming to enhance efficacy while mitigating adverse effects on osteogenic differentiation. In this study, an injectable sodium alginate (SA) hydrogel was fabricated by encapsulating titanium carbide powder (Ti₃C₂Tx) and osteoprotegerin Icariin (ICA) along with DOX. This hydrogel system demonstrated remarkable drug-loading capacity and sustained drug release. Furthermore, under near-infrared (NIR) irradiation, the hydrogel displayed outstanding photothermal effects, which, in conjunction with chemotherapy and phototherapy, effectively eradicated UMR-106 tumor cells in vitro. The incorporation of ICA not only enhanced the anti-tumor effect but also alleviated the adverse effects of DOX on the osteogenic differentiation inhibition of bone marrow mesenchymal stem cells (BMSCs). In vivo, findings further confirmed that injectable ITD/SA hydrogels can synergistically heighten anti-osteosarcoma effectiveness while mitigating local osteogenic toxicity. Given these benefits, this hydrogel holds extensive application prospects in the local therapy of OS.

Graphical Abstract

Schematic diagram of injectable NIR-responsive ITD/SA hydrogel phototherapy versus chemotherapy for OS and protection against BMSCS. (A) Illustration of the preparation process of the ITD/SA hydrogel. (B) Schematic of the therapeutic effect of ITD/SA under NIR irradiation.