Synthesis and potential osteogenic applications of Wnt3a-loaded ZIF-8 nanoparticles

作者全名："Wang, Hengfei; Chen, Song; He, Zihan; Chen, Junyu; Zhu, Zhou; Wan, Qianbing; Wang, Jian; Pei, Xibo"

作者地址："[Wang, Hengfei; Chen, Song; He, Zihan; Chen, Junyu; Zhu, Zhou; Wan, Qianbing; Wang, Jian; Pei, Xibo] Sichuan Univ, West China Hosp Stomatol, Natl Clin Res Ctr Oral Dis, State Key Lab Oral Dis,Dept Prosthodont, Chengdu 610041, Peoples R China; [Chen, Song] Chongqing Med Univ, Stomatol Hosp, Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing 401147, Peoples R China"

通信作者："Wang, J; Pei, XB (通讯作者)，Sichuan Univ, West China Hosp Stomatol, Natl Clin Res Ctr Oral Dis, State Key Lab Oral Dis,Dept Prosthodont, Chengdu 610041, Peoples R China."

来源：CHINESE CHEMICAL LETTERS

ESI学科分类：CHEMISTRY

WOS号：WOS:001165087200001

JCR分区：Q1

影响因子：9.1

年份：2024

卷号：35

期号：3

开始页：　

结束页：　

文献类型：Article

关键词：Metal-organic frameworks; Nanoparticle; Drug release; Osteogenesis; Bone defects

摘要："The Wnt signaling pathway plays a critical role in bone homeostasis, and the related protein therapy strategies have been reported to have great potential in osseointegration; however, they face formidable challenges such as complex external environments and unavoidable protein denaturation. In this work, we report a novel approach combining the synthesis of metal-organic frameworks (MOFs) and protein encapsulation in a one-pot process based on zeolitic imidazolate framework-8 (ZIF-8) and Wnt3a protein, with improved biomechanical behavior and enhanced protein biological response. This combination was designed to enhance the Wnt3a protein function through the improved chemical stability provided by the ZIF-8 crystals. Additionally, the zinc ions contained in the ZIF-8 crystals induced bone homeostasis, further favoring the osteogenesis. The results showed that the Wnt3a protein-loaded ZIF-8 crystals served as efficient drug delivery vehicles to promote osteogenesis, preventing protein denaturation. In particular, Wnt3a-loaded ZIF-8 nanoparticles (Wnt3a@ZIF-8 NPs) had higher efficacy on bone marrow mesenchymal stem cells (BMSCs) than ZIF-8 NPs or Wnt3a proteins, contributing to the osteogenesis through ZIF-8 crystals and intracellular Wnt3a proteins released from Wnt3a@ZIF-8 NPs. Furthermore, polymerase chain reaction (PCR) analysis showed that the osteogenic pathways were upregulated. Overall, the present onepot process can open up new avenues to develop signaling protein-delivery systems for applications in protein therapy strategies. (c) 2024 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences."

基金机构："National Nature Sci-ence Foundations of China [82271016, 82271034, 82270961, 82071164, 8197032972, 81901060]; Key research program of Sichuan Science and technology Department [2021YFS0052]; Research and Development Program (West China Hospital of Stom-atology, Sichuan University) [RD-03-202107, RD-03-202310]"

基金资助正文："This work was financially supported by National Nature Sci-ence Foundations of China (Nos. 82271016, 82271034, 82270961, 82071164, 8197032972, 81901060) , Key research program of Sichuan Science and technology Department (No. 2021YFS0052) , Research and Development Program (West China Hospital of Stom-atology, Sichuan University) (Nos. RD-03-202107, RD-03-202310) ."