The “vicious cycle” established between tumor growth and osteolysis aggravates the process of breast cancer bone metastasis, leading to life-threatening skeletal-related events that severely reduce survival and quality of life. To effectively interrupt the “vicious cycle”, innovative therapeutic strategies that not only reduce osteolysis but also relieve tumor burden are urgently needed. Herein, a bone-seeking moiety, alendronate (ALN), functionalized coordination polymer nanoparticles (DZ@ALN) co-delivering cisplatin prodrug (DSP) and antiresorptive agent zoledronate (ZOL) via Zn²⁺ crosslinking for combination therapy was reported. The versatile DZ@ALN with a diameter of about 40 nm can cross the fissure in the bone marrow sinus capillaries, and possesses an excellent bone-seeking ability both in vitro and in vivo. Additionally, DZ@ALN could synergistically inhibit the proliferation of cancer cells, suppress the formation of osteoclast-like cells and induce the apoptosis of osteoclasts in vitro. Importantly, it could preferentially accumulate in bone affected site, remarkably inhibit the proliferation of tumor cells, relieving bone pain, and significantly inhibit the activation of osteoclasts, protecting the bone from destruction in vivo, eventually leading to the breakdown of “vicious cycle” without inducing obvious systemic toxicity. This innovative nanoagent combines chemotherapy and osteolysis inhibition, exhibiting an inspiring strategy for effective treatment of bone metastasis.

肿瘤生长和骨质溶解之间建立的“恶性循环”加剧了乳腺癌骨转移的过程，导致危及生命的骨骼相关事件，严重降低生存率和生活质量。为了有效中断“恶性循环”，迫切需要既能减少骨溶解又能减轻肿瘤负担的创新治疗策略。在此，寻骨部分阿仑膦酸盐 (ALN)、功能化配位聚合物纳米粒子 (DZ@ALN)通过Zn ²⁺共同递送顺铂前药 (DSP) 和抗吸收剂唑来膦酸盐 (ZOL)报道了用于联合治疗的交联。直径约40 nm的多功能DZ@ALN可以穿过骨髓窦毛细血管裂隙，在体外和体内均具有优异的寻骨能力。此外，DZ@ALN在体外可以协同抑制癌细胞增殖，抑制破骨细胞样细胞的形成，诱导破骨细胞凋亡。重要的是，它可以优先积聚在骨受累部位，显着抑制肿瘤细胞的增殖，缓解骨痛，并显着抑制破骨细胞的活化，保护骨在体内免受破坏，最终导致“恶性循环”的破裂，而不会引起明显的全身毒性。这种创新的纳米药物结合了化疗和骨溶解抑制，展示了一种有效治疗骨转移的鼓舞人心的策略。