Bakir Mohamad, Dawalibi Ahmad, Mufti Mohammad Alaa, Behiery Ayman, Mohammad Khalid S
Department of Medicine, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia.
Department of Anatomy, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia.
Pharmaceutics. 2025 May 2;17(5):603. doi: 10.3390/pharmaceutics17050603.
Bone metastases are a prevalent and debilitating consequence of various cancers, including breast and prostate carcinomas, which significantly compromise patient quality of life due to pain, fractures, and other skeletal-related events (SREs). This review examines the pathophysiology of bone metastases, emphasizing the role of the bone microenvironment in tumor progression through mechanisms such as osteotropism and the dysregulated bone remodeling cycle. The primary focus is on the emerging nano-drug delivery systems (DDS) designed to target the bone microenvironment and improve the therapeutic index of anticancer agents. Current treatments, mainly comprising bisphosphonates and radiotherapy, provide palliative benefits but often have limited efficacy and significant side effects. Innovative strategies, such as bisphosphonate-conjugated nanoparticles and targeted therapies that utilize the unique bone marrow niche, are explored for their potential to enhance drug accumulation at metastatic sites while minimizing systemic toxicity. These approaches include the use of liposomes, polymeric nanoparticles, and inorganic nanoparticles, which can be functionalized to exploit the biological barriers within the bone microenvironment. This review also discusses the challenges and future directions for nano-DDS in clinical settings, emphasizing the need for multidisciplinary research to effectively integrate these technologies into standard care protocols.
骨转移是包括乳腺癌和前列腺癌在内的多种癌症常见且使人衰弱的后果，由于疼痛、骨折和其他骨相关事件（SREs），它会严重损害患者的生活质量。本综述探讨了骨转移的病理生理学，强调了骨微环境在肿瘤进展中的作用，其机制包括亲骨性和失调的骨重塑周期。主要关注点是新兴的纳米药物递送系统（DDS），其旨在靶向骨微环境并提高抗癌药物的治疗指数。目前的治疗方法主要包括双膦酸盐和放疗，虽能提供姑息性疗效，但往往疗效有限且副作用显著。探索了创新策略，如双膦酸盐偶联纳米颗粒以及利用独特骨髓生态位的靶向疗法，它们具有增强药物在转移部位蓄积同时将全身毒性降至最低的潜力。这些方法包括使用脂质体、聚合物纳米颗粒和无机纳米颗粒，它们可以进行功能化修饰以利用骨微环境中的生物屏障。本综述还讨论了纳米DDS在临床应用中的挑战和未来方向，强调了多学科研究的必要性，以便将这些技术有效整合到标准护理方案中。
