Aminopeptidase‐N‐activated Theranostic Prodrug for NIR Tracking of Local Tumor Chemotherapy. (20th September 2018)

• Record Type: Journal Article
• Authors: Xiao, Ming; Sun, Wen; Fan, Jiangli; Cao, Jianfang; Li, Yueqing; Shao, Kun; Li, Miao; Li, Xiaojing; Kang, Yao; Zhang, Wendi; Long, Saran; Du, Jianjun; Peng, Xiaojun
• Is Part Of: Advanced functional materials. Volume 28:Number 47(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-09-20
• Subjects: cancer diagnosis -- enzyme activation -- NIR tracking -- theranostic prodrugs -- tumor chemotherapy; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adfm.201805128
• Languages: English
• ISSNs: 1616-301X

Abstract

Abstract: The development of molecular theranostic prodrugs for in vivo cancer diagnosis and targeted chemotherapy is urgently required. Enzyme‐activated prodrugs display superior selectivity as a result of cancer‐specific enzymes which serve as cancer biomarkers. Herein, an aminopeptidase N (APN)‐activated theranostic prodrug Nile blue‐C6 ‐amide‐ p ‐fluorophenylalanyl‐l ‐melphalanyl (NBFMel ) is reported for fluorescence cancer diagnosis and local tumor treatment.NBFMel demonstrates negligible cytotoxicity and very weak fluorescence due to the photoinduced electron transfer (PET) between melphalan and Nile blue fluorophore. After activation caused by APN, the prodrug releases free melphalan that inhibits tumor cell growth. Simultaneously, the reaction blocks the PET process and switches on the fluorescence, which can be used for cancer diagnosis.NBFMel is successfully utilized to report the presence of tumor and for in situ tracking of drug release in tumor‐bearing mouse models. Moreover, NBFMel demonstrates efficient tumor inhibition when intravenously injected into mice. Therefore, the APN‐activated theranostic prodrug provides a new platform for in vivo cancer diagnosis and targeted anticancer chemotherapy. Abstract : An aminopeptidase‐N‐(APN)‐activated prodrug is developed through conjugation of a fluorophore and an anticancer drug. The prodrug can be activated by APN to release free drug that inhibits tumor cell growth, and switches on the fluorescence for cancer diagnosis. Moreover, the prodrug demonstrates efficient tumor inhibition in living mice with negligible systemic toxicity compared to the free drug.