Integration of Bone-Targeted Delivery and Crosstalk Modulation of Liver-Bone Axis for Improved Osteoporosis Therapy

IF 16 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
ACS Nano Pub Date : 2025-06-24 DOI:10.1021/acsnano.5c05460
Yunhao You, Shaoqiu Leng, Jie Shi, Han Yang, Mingzheng Chang, Qingliang Ma, Dapeng Zhang, Haochen Sun, Lianlei Wang*, Zhiliang Gao*, Jiwei Cui* and Xinyu Liu*, 
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引用次数: 0

Abstract

Nanomedicines hold great promise for the treatment of osteoporosis, while their nonspecific accumulation in the liver typically reduces the drug delivery efficacy. Herein, we report bone-targeted liposomes encapsulated with arginine and metformin for the treatment of osteoporosis. These liposomes are functionalized with alendronate to enhance the bone-targeting capability. The delivered agents directly modulate osteoblasts, osteoclasts, and osteocytes, promoting bone formation and inhibiting bone resorption to counteract osteoporotic bone loss. In addition to targeted bone delivery, the inevitable hepatic accumulation of liposomes is strategically utilized to stimulate the hepatic secretion of lecithin-cholesterol acyltransferase (LCAT), which, in turn, promotes bone remodeling by engaging the liver-bone axis. This dual mechanism, which combines targeted bone delivery with beneficial off-target hepatic effects, synergistically enhances therapeutic outcomes. Our findings highlight a promising nanomedicine-based strategy that takes advantage of interorgan communication to optimize osteoporosis treatment.

Abstract Image

骨靶向递送和肝-骨轴串扰调节的整合改善骨质疏松症治疗。
纳米药物在治疗骨质疏松症方面具有很大的前景,但它们在肝脏中的非特异性积累通常会降低药物的递送效果。在此,我们报告骨靶向脂质体包被精氨酸和二甲双胍治疗骨质疏松症。这些脂质体被阿仑膦酸钠功能化以增强骨靶向能力。所递送的药物直接调节成骨细胞、破骨细胞和骨细胞,促进骨形成,抑制骨吸收,以对抗骨质疏松性骨质流失。除了靶向骨递送外,脂质体不可避免的肝脏积聚被策略性地利用来刺激肝脏卵磷脂-胆固醇酰基转移酶(LCAT)的分泌,这反过来又通过参与肝-骨轴促进骨重塑。这种双重机制结合了靶向骨输送和有益的脱靶肝脏效应,协同提高了治疗效果。我们的研究结果强调了一种有前途的基于纳米医学的策略,利用器官间的交流来优化骨质疏松症的治疗。
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来源期刊
ACS Nano
ACS Nano 工程技术-材料科学:综合
CiteScore
26.00
自引率
4.10%
发文量
1627
审稿时长
1.7 months
期刊介绍: ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.
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