Black phosphorus (BPs) nanosheets with their inherent and selective chemotherapeutic effects have recently been identified as promising cancer therapeutic agents, but challenges in surface functionalization hinder satisfactory enhancement of their selectivity between tumors and normal cells. To address this issue, we developed a novel biomineralization-inspired strategy to synthesize CaBPs-Na₂FDP@CaCl₂ nanosheets, aiming to achieve enhanced and selective anticancer bioactivity along with accelerated osteoblast activity. Benefiting from the in situ mineralization and fructose modification, CaBPs-Na₂FDP@CaCl₂ exhibited improved pH-responsive degradation behavior and targeted therapy for osteosarcoma. The in vitro results indicated that CaBPs-Na₂FDP@CaCl₂ exhibited efficient uptake and quick degradation by GLUT5-positive 143B osteosarcoma cells, enhancing BPs-driven chemotherapeutic effects through ATP level disturbance-mediated apoptosis of tumor cells. Moreover, CaBPs-Na₂FDP@CaCl₂ underwent gradual degradation into PO₄³⁻, Ca²⁺ and fructose in MC3T3-E1 cells, eliminating systemic toxicity. Intracellular Ca²⁺ bound to calmodulin (CaM), activating Ca²⁺/CaM-dependent signaling cascades, thereby enhancing osteoblast differentiation and mineralization in pro-osteoblastic cells. In vivo experiments affirmed the anti-tumor capability, inhibition of tumor recurrence and bone repair promotion of CaBPs-Na₂FDP@CaCl₂. This study not only broadens the application of BPs in bone tumor therapy but also provides a versatile surface functionalization strategy for nanotherapeutic agents.

中文翻译：

---

果糖矿化黑磷用于融合骨再生和肿瘤抑制

黑磷（BPs）纳米片以其固有的选择性化疗作用最近被认为是有前途的癌症治疗剂，但表面功能化的挑战阻碍了其在肿瘤和正常细胞之间选择性的令人满意的增强。为了解决这个问题，我们开发了一种新的生物矿化启发策略来合成CaBPs-Na ₂ FDP@CaCl ₂纳米片，旨在实现增强和选择性的抗癌生物活性以及加速的成骨细胞活性。受益于原位矿化和果糖修饰，CaBPs-Na ₂ FDP@CaCl ₂表现出改善的pH响应性降解行为和骨肉瘤的靶向治疗。体外结果表明，CaBPs-Na ₂ FDP@CaCl ₂被GLUT5阳性143B骨肉瘤细胞有效摄取和快速降解，通过ATP水平扰动介导的肿瘤细胞凋亡增强BPs驱动的化疗效果。此外，CaBPs-Na ₂ FDP@CaCl ₂在MC3T3-E1细胞中逐渐降解为PO ₄ ³⁻、Ca ²⁺和果糖，消除了全身毒性。细胞内Ca ²⁺与钙调蛋白(CaM) 结合，激活Ca ²⁺ /CaM 依赖性信号级联，从而增强前成骨细胞中的成骨细胞分化和矿化。体内实验证实了CaBPs-Na ₂ FDP@CaCl ₂的抗肿瘤能力、抑制肿瘤复发和促进骨修复的能力。这项研究不仅拓宽了BP在骨肿瘤治疗中的应用，而且为纳米治疗剂提供了一种多功能的表面功能化策略。