An acid-responsive bone-targeting nanoplatform loaded with curcumin balances osteogenic and osteoclastic functions

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.