在女性中，乳腺癌 (BC) 是最常见的癌症，尽管诊断和治疗取得了进步，但 20-30% 的早期 BC 患者会出现转移性疾病。转移性BC被认为是一种不治之症，占BC相关死亡的90%，只有26%的转移性患者达到5年生存率。因此，对于预防或治疗早期乳腺癌患者的转移的需求尚未得到满足。双膦酸盐 (BP) 是骨吸收的有效抑制剂，广泛用于预防骨质疏松症和其他骨骼疾病，以及治疗 BC 患者的继发性骨癌。此外，BP 的直接抗癌活性已在原发性肿瘤模型中得到证实。然而，这些研究受到限制，因为需要远远高于临床范围的剂量，以克服 BP 对骨骼的高亲和力和在肿瘤本身的积聚不良，这会导致毒性，包括颌骨坏死。为了减少 BP 剂量、提高生物利用度和直接抗癌活性，我们使用 RALA (R-) 肽递送系统与含氮 BP 利塞膦酸盐 (R-RIS) 形成高度稳定的纳米颗粒。体外研究表明，与 RIS 相比，R-RIS 纳米颗粒增加了细胞毒性并减少了转移性 BC 细胞的增殖、迁移、侵袭和粘附等转移特征。此外，在体内模型中，R-RIS 增加了肿瘤积累，同时仍保持与单独 RIS 相似的骨积累。肿瘤积累的增加与肿瘤体积和肺转移的减少相对应。 R-RIS 具有与标准化疗联合用于治疗原发性 BC 及其转移的巨大潜力，同时仍具有骨吸收抑制特性。

In women, breast cancer (BC) is the most common cancer, and despite advancements in diagnosis and treatment, 20-30% of early stage BC patients develop metastatic disease. Metastatic BC is deemed an incurable disease, which accounts for 90% of BC related deaths, with only 26% of metastatic patients reaching a 5 year survival rate. Therefore, there is an unmet need for the prevention or treatment of metastasis in early stage breast cancer patients. Bisphosphonates (BPs) are potent inhibitors of bone resorption and are extensively used for the prevention of osteoporosis and other skeletal disorders, as well as for the treatment of secondary bone cancer in BC patients. Furthermore, the direct anticancer activity of BPs has been established in primary tumor models. However, these studies were limited by the need for dosages far above the clinical range to overcome BPs' high affinity for bones and poor accumulation in the tumor itself, which leads to toxicity, including osteonecrosis of the jaw. To decrease BP dosage, increase bioavailability, and direct anticancer activity, we used the RALA (R-) peptide delivery system to form highly stable NPs with the nitrogen containing BP, risedronate (R-RIS). In vitro studies showed that, in comparison to RIS, R-RIS nanoparticles increased cytotoxicity and reduced metastatic features such as proliferation, migration, invasion, and adhesion of metastatic BC cells to bones. Furthermore, in an in vivo model, R-RIS had increased tumor accumulation while still maintaining similar bone accumulation to RIS alone. This increase in tumor accumulation corresponded with decreased tumor volume and lungs metastasis. R-RIS has great potential to be used in combination with standard of care chemotherapy for the treatment of primary BC and its metastasis while still having its bone resorption inhibiting properties.