The construction of a functional drug delivery system to reverse the multidrug resistance (MDR) of bone tumors in cases of failed chemotherapy remains a challenge. Herein, we demonstrate a selenium-doped calcium phosphate (Se-CaP) biomineral with high biocompatibility, biodegradability and pH-sensitive drug release properties. Se-CaP may not only serve as an effective drug-carrier to enhance the uptake of doxorubicin (DOX), but may also synchronously induce caspases-mediated apoptosis of osteosarcoma by generating intracellular reactive oxygen species (ROS). Furthermore, in vitro and in vivo studies obviously demonstrate that Se-CaP can reverse the MDR of osteosarcoma by down-regulating the expression of MDR-related ABC (ATP binding cassette) transporters proteins (ABCB1 and ABCC1). Finally, DOX-loaded Se-CaP can significantly inhibit DOX-resistant MG63 (MG63/DXR) tumor growth in nude mice. Considering its biomimetic chemical properties, the Se-CaP biomineral, with the multiple functions mentioned above, could be a promising candidate for treating bone tumors with MDR characteristics.

在化疗失败的情况下，构建功能性药物递送系统以逆转骨肿瘤的多药耐药性（MDR）仍然是一个挑战。进来吧，我们展示了一种掺硒磷酸钙 (Se-CaP) 生物矿物，具有高生物相容性、生物降解性和 pH 敏感的药物释放特性。Se-CaP 不仅可以作为一种有效的药物载体来增强阿霉素 (DOX) 的摄取，还可以通过产生细胞内活性氧 (ROS) 同步诱导半胱天冬酶介导的骨肉瘤凋亡。此外，体外和体内研究明显表明，Se-CaP 可以通过下调 MDR 相关 ABC（ATP 结合盒）转运蛋白（ABCB1 和 ABCC1）的表达来逆转骨肉瘤的 MDR。最后，载有 DOX 的 Se-CaP 可显着抑制裸鼠体内 DOX 抗性 MG63 (MG63/DXR) 肿瘤的生长。考虑到其仿生化学特性，具有上述多种功能的 Se-CaP 生物矿物可能是治疗具有 MDR 特征的骨肿瘤的有希望的候选者。