骨粗鬆症の標的閉経後治療のためのクルクミン送達担体としての骨芽細胞様細胞膜で被覆されたナノ粒子

Postmenopausal osteoporosis, driven by estrogen-deficient bone loss, faces therapeutic challenges due to current drug side effects and off-target effects. While curcumin demonstrates dual osteogenic and antiresorptive activity, its clinical translation is hindered by poor aqueous solubility, chemical instability, and photolability. A bone-targeted delivery system using osteoblast-like cell membrane-coated nanoparticles was designed to enhance precision and efficacy for treating osteoporosis. Through systematic database analysis, osteoblast-like cell membrane containing CXCR4 and TNF-α receptors were selected to coat curcumin-loaded PLGA nanoparticles (Cur@NPs), namely OM/Cur@NPs. OM/Cur@NPs and Cur@NPs were injected into ovariectomized (OVX) mice to comparatively assess in vivo bone-targeting. Additionally, leveraging the specific binding capability of TNFR to TNF-α, we evaluated the effects of cell membrane-coated nanoparticles on osteoblasts and osteoclasts formation under TNF-α stimulation in vitro. We further evaluated the anti-osteoporotic efficacy of OM/Cur@NPs in vivo by micro-CT analysis (BMD, Tb.BV/TV, Tb.N, Tb.Th, Tb.Sp) and histological examination of bone formation and resorption. The OM/Cur@NPs group exhibited higher bone accumulation compared to Cur@NPs in OVX mice. Notably, these biomimetic nanoparticles neutralized TNF-α, thereby enhancing osteoblastic functions, while attenuating the synergistic pro-osteoclastogenic effects of TNF-α and RANKL. In vivo studies demonstrated that the OM/Cur@NPs-treated group showed superior radiographic bone parameters (BMD, Tb.BV/TV, Tb.N, Tb.Th, Tb.Sp) compared to other experimental groups. Furthermore, histological examination revealed the dual efficacy of OM/Cur@NPs in enhancing bone formation while inhibiting bone resorption in osteoporotic mice. This dual-functional platform couples targeted drug delivery with inflammatory microenvironment modulation and holds promise for metabolic bone disorders.