Ma Shiqing, Xu Shendan, Li Minting, Du Yaqi, Tian Guangjie, Deng Jiayin, Zhang Wenyi, Wei Pengfei, Zhao Bo, Zhang Xuesong, Liu Zihao, Wang Yonglan
Department of Stomatology, The Second Hospital of Tianjin medical university, Tianjin, 300211, China.
School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 30070, China.
Adv Healthc Mater. 2023 Oct;12(25):e2300560. doi: 10.1002/adhm.202300560. Epub 2023 Aug 18.
Restoring bone homeostasis is the key to the treatment of osteoporosis. How to increase osteogenic ability or inhibit osteoclast activity has always been a topic of great concern. In recent years, short peptides with biological activity have received great attention in bone repair. However, the application of short peptides is still limited due to the lack of a stable and targeted delivery system. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles modified by alendronate (AL) to transport osteogenic peptides (OGP) (AL-PLGA@P NPs) are designed. Benefiting from the high affinity of AL for hydroxyapatite, AL-PLGA@P NPs have the ability to target bone. In this delivery system, OGP that promotes osteogenesis synergizes with AL, which inhibits osteoclasts, to regulate bone homeostasis, which gives them more advantages in the treatment of osteoporosis. The data shows that nanoparticles can selectively deliver peptides to the bone surface without systemic toxicity. Moreover, nanoparticles can upregulate osteogenesis-related factors (ALP, Runx-2, and BMP2) and downregulate osteoclast-related factors (TRAP and CTSK) in vitro. With AL-PLGA@P NPs, bone microarchitecture and bone mass are improved in ovariectomized osteoporosis rats. Therefore, this study proposes a novel osteoporosis-based drug system that effectively improves bone density.
恢复骨稳态是治疗骨质疏松症的关键。如何提高成骨能力或抑制破骨细胞活性一直是备受关注的话题。近年来，具有生物活性的短肽在骨修复方面受到了极大关注。然而，由于缺乏稳定且靶向的递送系统，短肽的应用仍然有限。设计了用阿仑膦酸盐（AL）修饰的聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒来转运成骨肽（OGP）（AL-PLGA@P NPs）。得益于AL对羟基磷灰石的高亲和力，AL-PLGA@P NPs具有靶向骨的能力。在这个递送系统中，促进成骨的OGP与抑制破骨细胞的AL协同作用，以调节骨稳态，这使其在骨质疏松症治疗中具有更多优势。数据表明，纳米颗粒可以将肽选择性地递送至骨表面而无全身毒性。此外，纳米颗粒在体外可上调成骨相关因子（碱性磷酸酶、Runx-2和骨形态发生蛋白2）并下调破骨细胞相关因子（抗酒石酸酸性磷酸酶和组织蛋白酶K）。使用AL-PLGA@P NPs可改善去卵巢骨质疏松大鼠的骨微结构和骨量。因此，本研究提出了一种有效提高骨密度的新型骨质疏松症药物系统。
