Multiple myeloma (MM) is the second most prevalent hematological malignancy. Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy. This study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy, which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes, termed T-PB@M. The results from our investigations highlight the considerable bone affinity of T-PB@M, both in vitro and in vivo. Additionally, this material demonstrated a capability for drug release triggered by low pH conditions. Moreover, T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose) polymerase 1 (PARP1)–Caspase-3–B-cell lymphoma-2 (Bcl-2) pathway in MM cells. Notably, T-PB@M preferentially targeted bone-involved sites, thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic mice. Therefore, this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM.

多发性骨髓瘤（MM）是第二常见的血液恶性肿瘤。目前的多发性骨髓瘤治疗策略受到全身毒性和次优治疗效果的阻碍。本研究通过开发有效的 MM 靶向化疗策略来解决这些局限性，该策略利用阿仑膦酸钠与骨基质中羟基磷灰石的高结合亲和力以及骨髓瘤细胞膜的同源靶向（称为 T-PB@M）。我们的研究结果强调了 T-PB@M在体外和体内都具有相当大的骨亲和力。此外，该材料还表现出在低 pH 条件下触发药物释放的能力。此外，T-PB@M 在 MM 中通过聚（ADP-核糖）聚合酶 1 (PARP1)–Caspase-3–B 细胞淋巴瘤-2 (Bcl-2) 途径诱导活性氧的产生并引发细胞凋亡细胞。值得注意的是，T-PB@M 优先靶向骨相关部位，从而避免全身毒副作用并延长 MM 原位小鼠的存活时间。因此，这种设计的靶MM纳米载体为MM的精准治疗提供了一个有前途且潜在有效的平台。