Letrozole-Based Near-Infrared Dynamic Imaging Targeting Ductal-Vascular RhoJ From Pancreatic Intraepithelial Neoplasia to Pancreatic Ductal Adenocarcinoma

Cao, Zhi1,2,3; Hu, Zhuang2; Wang, Yishu3; Zhao, Fengyun4; Li, Jingmin5; Li, Ruihan2; Hu, Weibin3; Liu, Bei3; Tang, Shaohui6; Wang, Ping7; Li, Fugui4; Chen, Zilin2; Wang, Lisheng1; Ma, Xiaodong3

2024-09-01

10.1002/adhm.202402913

ADVANCED HEALTHCARE MATERIALS   影响因子和分区

2192-2640

2192-2659

["Pancreatic ductal adenocarcinoma (PDAC) relies heavily on neoangiogenesis for its progression, making early detection crucial. Here, LTZi-MHI148 (Letrozole inhibitor bonding with MHI-148 dye), a near-infrared (NIR) fluorescent agent is developed, to target RhoJ (Ras Homolog Family Member J), a protein expressed in neonatal vasculature, for both imaging and therapy of early PDAC. This agent is synthesized by conjugating Letrozole with MHI-148, exhibiting excellent NIR characteristics and photostability. In vitro studies showed that LTZi-MHI148 selectively accumulated within pancreatic cancer cells through Organic Anion Transporting Polypeptide (OATP) transporters and bound to cytoplasmic RhoJ. In vivo, the probe effectively targeted neoangiogenesis and Pancreatic Intraepithelial Neoplasias (PanINs) in various PDAC models, including the orthotopic, ectopic, spontaneous, and tamoxifen-induced tumors. Notably, LTZi-MHI148 detected preneoplastic PanIN lesions with Overexpressed RhoJ and active neoangiogenesis in both spontaneous and tamoxifen-induced PDAC murine models. Longitudinal imaging studies revealed that RhoJ-targeted neoangiogenesis tracks lesion progression, highlighting LTZi-MHI148's utility in monitoring disease progression. Furthermore, multiple LTZi-MHI148 administrations attenuated PanINs to PDAC progression, suggesting its potential as a therapeutic intervention. These findings underscore the translational potential of LTZi-MHI148 for the early detection and targeted therapy of PDAC, utilizing NIR-I/II imaging to monitor RhoJ overexpression in precancerous ductal neoplasia associated with neoangiogenesis.","In article 2402913, Zhi Cao and co-workers develop a near-infrared fluorescent probe named LTZi-MHI148 that specifically targets the RhoJ protein in pancreatic ductal adenocarcinoma (PDAC) for early detection and potential therapy. Moreover, we clearly validate that overexpressed RhoJ is inseparable from neoplastic ductal alterations and angiogenesis, demonstrating this agent can effectively inhibit these two processes. image"]

dynamic imaging LTZi-MHI148 near-infrared theranosis pancreatic ductal adenocarcinoma RhoJ

SCI

英语

第一 ; 通讯

National Natural Science Foundation of China["82072697","82073808"] ; National Natural Science Foundation of China (NSFC)[JCYJ20220530151810024]

Engineering ; Science & Technology - Other Topics ; Materials Science

Engineering, Biomedical ; Nanoscience & Nanotechnology ; Materials Science, Biomaterials

WOS:001321485000001

WILEY

Web of Science

1.Jinan Univ, Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1,Clin Med Coll 2,Dept Gastroenter, Shenzhen 518020, Guangdong, Peoples R China
2.Wuhan Univ, Sch Pharmaceut Sci, Wuhan 430071, Hubei, Peoples R China
3.South China Normal Univ, Inst Brain Res & Rehabil, Key Lab Brain Cognit & Educ Sci, Minist Educ China, Guangzhou 510631, Guangdong, Peoples R China
4.Zhongshan City Peoples Hosp, Canc Res Inst Zhongshan City, Zhongshan 528403, Guangdong, Peoples R China
5.Guangzhou women & childrens Med Ctr, Internal Med Dept, Guangzhou 510620, Guangdong, Peoples R China
6.First Affiliated Hosp Jinan Univ, Dept Gastroenterol, Guangzhou 510630, Guangdong, Peoples R China
7.Guangzhou Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Guangzhou 510120, Guangdong, Peoples R China

Cao, Zhi,Hu, Zhuang,Wang, Yishu,et al. Letrozole-Based Near-Infrared Dynamic Imaging Targeting Ductal-Vascular RhoJ From Pancreatic Intraepithelial Neoplasia to Pancreatic Ductal Adenocarcinoma[J]. ADVANCED HEALTHCARE MATERIALS,2024.

Cao, Zhi.,Hu, Zhuang.,Wang, Yishu.,Zhao, Fengyun.,Li, Jingmin.,...&Ma, Xiaodong.(2024).Letrozole-Based Near-Infrared Dynamic Imaging Targeting Ductal-Vascular RhoJ From Pancreatic Intraepithelial Neoplasia to Pancreatic Ductal Adenocarcinoma.ADVANCED HEALTHCARE MATERIALS.

Cao, Zhi,et al."Letrozole-Based Near-Infrared Dynamic Imaging Targeting Ductal-Vascular RhoJ From Pancreatic Intraepithelial Neoplasia to Pancreatic Ductal Adenocarcinoma".ADVANCED HEALTHCARE MATERIALS (2024).