Construction of 89Zr-Radiolabeled Melanin-Based Nanoprobes with FAP-Targeted Motifs for Tumor PET Imaging
文献类型：期刊论文
| 作者 | Wei, Xiaonan1,2,7; Lai, Chaoquan2,3; Zhu, Xiaoyang2,4; Ji, Aiyan2; Qin, Yeshan2; Gao, Shu2,6; Liu, Qiuyu5; Li, Yonghao2,6; Zhao, Xuanyan2,4; Lou, Hongyue2 |
| 刊名 | MOLECULAR PHARMACEUTICS
 |
| 出版日期 | 2025-11-03 |
| 卷号 | 22期号:11页码:7099-7110 |
| 关键词 | fibroblast activationprotein melanin nanoparticles FAPI PETimaging |
| ISSN号 | 1543-8384 |
| DOI | 10.1021/acs.molpharmaceut.5c01192 |
| 英文摘要 | Fibroblast activation protein (FAP) is an important target for the integrated diagnosis and treatment of tumors. However, FAP-targeted small molecule-based radiopharmaceuticals often face challenges such as low tumor uptake and short tumor retention, which hinder their biomedical and clinical applications. In this study, two radiolabeled FAP-targeted nanoprobes based on melanin nanoparticles (MNPs) were designed and developed in order to evaluate their potential for FAP-targeted theranostics. The excellent metal ion complexing property of melanin allowed 89Zr to be efficiently labeled on the MNP platform. After PEGylated MNPs were modified with small molecules FAPI-04 and GPFAPI-04 and radiolabeled with 89Zr to obtain [89Zr]Zr-F-MNPs and [89Zr]Zr-GPF-MNPs, these two nanoprobes achieved active targeting through FAPI ligands. The radiochemical purity of 89Zr-labeled nanoprobes remained above 90% in fetal bovine serum (FBS) solution in 72 h. In vitro experiments showed that both [89Zr]Zr-F-MNPs and [89Zr]Zr-GPF-MNPs were taken up by FAP high-expressing U87MG cells (2.58 +/- 0.07% vs 3.00 +/- 0.10% for 2 h; 2.93 +/- 0.08% vs 3.62 +/- 0.04% for 4 h). For the in vivo study, at 48 h postinjection (p.i.) of the nanoprobe, the U87MG tumor uptake of [89Zr]Zr-F-MNPs and [89Zr]Zr-GPF-MNPs reached 4.83 +/- 0.50% ID/g and 5.13 +/- 0.38% ID/g, respectively. Blocking experiments further confirmed the FAP-dependent targeting ability. Neither of the two nanoprobes elicited observable adverse effects in vivo. In conclusion, the FAPI-MNPs-based nanoprobe platform, which integrates active targeting and passive accumulation, improves tumor uptake and retention time of FAP-targeted radioligands with excellent biosafety. This study offers a new strategy and platform for the development of FAP-targeted diagnostic and therapeutic probes with promising clinical translation potential. |
| WOS关键词 | NANOPARTICLE ; CANCER ; CHALLENGES ; PROTEIN ; PROBE |
| 资助项目 | National Natural Science Foundation of China[U2267221] ; National Natural Science Foundation of China[82472091] ; Shanghai Municipal Science and Technology Major Project[TM202301H003] ; State Key Laboratory of Drug Research[SIMM0120231004] ; Gansu Science and Technology Major Project[23ZDFA014] ; Ningbo Major Research and Development Plan Project[2024Z214] ; Natural Science Foundation of Shanghai[24ZR1477300] ; Shandong Laboratory Program[SYS202205] |
| WOS研究方向 | Research & Experimental Medicine ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001596597900001 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/320715]  |
| 专题 | 国家级研究中心_原创新药研究全国重点实验室 |
| 通讯作者 | Lou, Hongyue; Qu, Chunrong; Cheng, Zhen |
| 作者单位 | 1.Shandong First Med Univ & Shandong Acad Med Sci, Jinan 250117, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Mol Imaging Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Northeastern Univ, Inst Mol Med, Coll Life & Hlth Sci, Shenyang 110169, Peoples R China 4.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 5.Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Radiol, Wuhan 430030, Peoples R China 6.Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China 7.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wei, Xiaonan,Lai, Chaoquan,Zhu, Xiaoyang,et al. Construction of 89Zr-Radiolabeled Melanin-Based Nanoprobes with FAP-Targeted Motifs for Tumor PET Imaging[J]. MOLECULAR PHARMACEUTICS,2025,22(11):7099-7110. |
| APA | Wei, Xiaonan.,Lai, Chaoquan.,Zhu, Xiaoyang.,Ji, Aiyan.,Qin, Yeshan.,...&Cheng, Zhen.(2025).Construction of 89Zr-Radiolabeled Melanin-Based Nanoprobes with FAP-Targeted Motifs for Tumor PET Imaging.MOLECULAR PHARMACEUTICS,22(11),7099-7110. |
| MLA | Wei, Xiaonan,et al."Construction of 89Zr-Radiolabeled Melanin-Based Nanoprobes with FAP-Targeted Motifs for Tumor PET Imaging".MOLECULAR PHARMACEUTICS 22.11(2025):7099-7110. |
入库方式： OAI收割
来源：上海药物研究所
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