A Bone-targeting near-infrared luminescence nanocarrier facilitates alpha-ketoglutarate efficacy enhancement for osteoporosis therapy

doi:10.1016/j.actbio.2023.11.022

	A Bone-targeting near-infrared luminescence nanocarrier facilitates alpha-ketoglutarate efficacy enhancement for osteoporosis therapy
	Cheng, Chunan 1,2; Xing, Zhenyu3 ; Hu, Qian3 ; Kong, Na3 ; Liao, Chongshan 2,4; Xu, Sixin3 ; Zhang, Jieying3 ; Kang, Feiwu 1,2; Zhu, Xingjun3
	2023-11
发表期刊	ACTA BIOMATERIALIA (IF:9.4[JCR-2023],9.9[5-Year])
ISSN	1742-7061
EISSN	1878-7568
卷号	173 页码:442-456
发表状态	已发表
DOI	10.1016/j.actbio.2023.11.022
摘要	Osteoporosis (OP), which largely increases the risk of fractures, is the most common chronic degenerative orthopedic disease in the elderly due to the imbalance of bone homeostasis. Alpha-ketoglutaric acid (AKG), an endogenous metabolic intermediate involved in osteogenesis, plays critical roles in osteogenic differentiation and mineralization and the inhibition of osteoclastogenic differentiation. However, the low bioavailability and poor bone-targeting efficiency of AKG seriously limit its efficacy in OP treatment. In this work, a bone-targeting, near-infrared emissive lanthanide luminescence nanocarrier loaded with AKG (β-NaYF4:7%Yb, 60%Nd@NaLuF4@mSiO2-EDTA-AKG, abbreviated as LMEK) is developed for the enhancement of AKG efficacy in OP therapy. By utilizing the NIR-II luminescence (>1000 nm) of LMEK, whole-body bone imaging with high spatial resolution is achieved to confirm the bone enrichment of AKG noninvasively in vivo. The results reveal that LMEK exhibits a remarkable OP therapeutic effect in improving the osseointegration of the surrounding bone in the ovariectomized OP mice models, which is validated by the enhanced inhibition of osteoclast through hypoxia-inducible factor-1α suppression and promotion of osteogenic differentiation in osteoblast. Notably, the dose of AKG in LMEK can be reduced to only 0.2 % of the dose when pure AKG is used in therapy, which dramatically improves the bioavailability of AKG and mitigates the metabolism burden. This work provides a strategy to conquer the low utilization of AKG in OP therapy, which not only overcomes the challenges in AKG efficacy for OP treatment but also offers insights into the development and application of other potential drugs for skeletal diseases. Statement of significance: Alpha-ketoglutarate (AKG) is an intermediate within the Krebs cycle, participating in diverse metabolic and cellular processes, showing potential for osteoporosis (OP) therapy. However, AKG's limited bioavailability and inefficient bone-targeting hinder its effectiveness in treating OP. Herein, a near-infrared emissive nanocarrier is developed that precisely targets bones and delivers AKG, bolstering its effectiveness in OP therapy. Thanks to this efficient bone-targeting delivery, the AKG dosage is reduced to 0.2 % of the conventional treatment level. This marks the first utilization of a bone-targeting nanocarrier to amplify AKG's bioavailability and OP therapy efficacy. Furthermore, the mechanism of AKG-loaded nanocarrier regulating the biological behavior of osteoclasts and osteoblasts mediated is tentatively explored. © 2023 Acta Materialia Inc.
关键词	Biochemistry Bone Controlled drug delivery Disease control Infrared devices Luminescence Mammals Metabolism Targeted drug delivery Thermography (imaging) Alpha-ketoglutarate Bone targeting Drug delivery nanoparticle Ketoglutarate Nanocarriers Near Infrared Near-infrared Near-infrared imaging Osteogenic differentiation Osteoporosis therapy
URL	查看原文
收录类别	EI ; SCI
语种	英语
资助项目	National Natural Science Foundation of China["820 01945","820 010 08","82271013"] ; Shanghai Pujiang Program[20PJ1410700]
WOS研究方向	Engineering ; Materials Science
WOS类目	Engineering, Biomedical ; Materials Science, Biomaterials
WOS记录号	WOS:001141215100001
出版者	Acta Materialia Inc
EI入藏号	20235115231903
EI主题词	Diseases
EI分类号	461.2 Biological Materials and Tissue Engineering ; 741.1 Light/Optics ; 742.1 Photography ; 801.2 Biochemistry
原始文献类型	Journal article (JA)
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/346386
专题	物质科学与技术学院物质科学与技术学院_硕士生物质科学与技术学院_本科生物质科学与技术学院_博士生物质科学与技术学院_PI研究组_朱幸俊组
通讯作者	Kang, Feiwu; Zhu, Xingjun
作者单位	1.Stomatol Hosp, Dept Oral & Maxillofacial Surg, 399 Middle Yan Chang Rd, Shanghai 200072, Peoples R China 2.Tongji Univ, Shanghai Engn Res Ctr Tooth Restorat & Regenerat, Dent Sch, 399 Middle Yan Chang Rd, Shanghai 200072, Peoples R China 3.ShanghaiTech Univ, Sch Phys Sci & Technol, 393 Middle Huaxia Rd, Shanghai 201210, Peoples R China 4.Stomatol Hosp, Dept Orthodont, 399 Middle Yan Chang Rd, Shanghai 200072, Peoples R China
通讯作者单位	物质科学与技术学院
推荐引用方式 GB/T 7714	Cheng, Chunan,Xing, Zhenyu,Hu, Qian,et al. A Bone-targeting near-infrared luminescence nanocarrier facilitates alpha-ketoglutarate efficacy enhancement for osteoporosis therapy[J]. ACTA BIOMATERIALIA,2023,173:442-456.
APA	Cheng, Chunan.,Xing, Zhenyu.,Hu, Qian.,Kong, Na.,Liao, Chongshan.,...&Zhu, Xingjun.(2023).A Bone-targeting near-infrared luminescence nanocarrier facilitates alpha-ketoglutarate efficacy enhancement for osteoporosis therapy.ACTA BIOMATERIALIA,173,442-456.
MLA	Cheng, Chunan,et al."A Bone-targeting near-infrared luminescence nanocarrier facilitates alpha-ketoglutarate efficacy enhancement for osteoporosis therapy".ACTA BIOMATERIALIA 173(2023):442-456.