Liang Minhao, Zhou Lei, Li Juan, Liang Bin, Zhou Liangyun, Xue Fengfeng, Jiang Libo, Hong Wei
Shanghai Institute of Geriatrics and Gerontology, Huadong Hospital, Fudan University, Shanghai 200040, China.
Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital, Fudan University, Shanghai 200040, China.
Regen Biomater. 2025 May 5;12:rbaf028. doi: 10.1093/rb/rbaf028. eCollection 2025.
Postmenopausal osteoporosis (PMOP) is a predominant form of clinical osteoporosis. It has led to significant health and social burdens for older patients. Reestablishing the balance between osteogenic and osteoclastic is a crucial strategy for treating PMOP. Curcumin (Cur), a naturally derived polyphenolic substance, has gained recognition as a viable option for treating osteoporosis. Despite its potential, the clinical use of Cur is hindered by its limited bioavailability and the presence of side effects. Nanoparticles modified with aspartic acid octapeptide (ASP8) exhibit a strong affinity for bone tissue, facilitating targeted delivery. This study presents novel acid-responsive zeolite imidazolate framework-8 (ZIF) nanoparticles modified with ASP8 and loaded with Cur (Cur@ZIF@ASP8, CZA). Upon delivery by this nanoparticle drug delivery system, Cur can effectively regulate bone homeostasis, offering a potential therapeutic strategy for osteoporosis. This study demonstrated that CZA nanoparticles could successfully transport Cur to bone tissue without significant toxicity. Furthermore, nanoparticles promote bone formation and inhibit osteoclast activity. They also modify the expression of related genes and proteins, such as OCN, ALP, CTSK and MMP9. Significant evaluations utilizing microcomputed tomography, Masson's staining, hematoxylin and eosin staining and immunofluorescence staining demonstrated that intravenous CZA administration in ovariectomized mice resulted in bone destruction while simultaneously reducing overall bone loss. In conclusion, CZA nanoparticles hold promise as a therapeutic option for osteoporosis.
绝经后骨质疏松症（PMOP）是临床骨质疏松症的主要形式。它给老年患者带来了巨大的健康和社会负担。重建成骨细胞与破骨细胞之间的平衡是治疗PMOP的关键策略。姜黄素（Cur）是一种天然衍生的多酚类物质，已被公认为治疗骨质疏松症的可行选择。尽管有其潜力，但Cur的临床应用受到其有限的生物利用度和副作用的阻碍。用天冬氨酸八肽（ASP8）修饰的纳米颗粒对骨组织具有很强的亲和力，有助于靶向递送。本研究提出了用ASP8修饰并负载Cur的新型酸响应性沸石咪唑酯骨架-8（ZIF）纳米颗粒（Cur@ZIF@ASP8，CZA）。通过这种纳米颗粒药物递送系统给药后，Cur可以有效地调节骨稳态，为骨质疏松症提供了一种潜在的治疗策略。本研究表明，CZA纳米颗粒可以成功地将Cur转运到骨组织，而无明显毒性。此外，纳米颗粒促进骨形成并抑制破骨细胞活性。它们还改变相关基因和蛋白质的表达，如骨钙素（OCN）、碱性磷酸酶（ALP）、组织蛋白酶K（CTSK）和基质金属蛋白酶9（MMP9）。利用微型计算机断层扫描、Masson染色、苏木精和伊红染色以及免疫荧光染色进行的显著评估表明，在去卵巢小鼠中静脉注射CZA可导致骨破坏，同时减少总体骨丢失。总之，CZA纳米颗粒有望成为治疗骨质疏松症的一种选择。
