title: AMP-guided tumour-specific nanoparticle delivery via adenosine A1 receptor.
abstract: Active targeting-ligands have been increasingly used to functionalize nanoparticles for tumour-specific clinical applications. Here we utilize nucleotide adenosine 5'-monophosphate (AMP) as a novel ligand to functionalize polymer-based fluorescent nanoparticles (NPs) for tumour-targeted imaging. We demonstrate that AMP-conjugated NPs (NPs-AMP) efficiently bind to and are following internalized into colon cancer cell CW-2 and breast cancer cell MDA-MB-468 in vitro. RNA interference and inhibitor assays reveal that the targeting effects mainly rely on the specific binding of AMP to adenosine A1 receptor (A1R), which is greatly up-regulated in cancer cells than in matched normal cells. More importantly, NPs-AMP specifically accumulate in the tumour site of colon and breast tumour xenografts and are further internalized into the tumour cells in vivo via tail vein injection, confirming that the high in vitro specificity of AMP can be successfully translated into the in vivo efficacy. Furthermore, NPs-AMP exhibit an active tumour-targeting behaviour in various colon and breast cancer cells, which is positively related to the up-regulation level of A1R in cancer cells, suggesting that AMP potentially suits for more extensive A1R-overexpressing cancer models. This work establishes AMP to be a novel tumour-targeting ligand and provides a promising strategy for future diagnostic or therapeutic applications.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Tongcheng
authors.initials: T
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Fajun
authors.initials: F
authors.lastname: Han
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China; Shanghai Collaborative Innovation Center for Biomanufacturing Technology, Shanghai 200237, China.
authors.forename: Yuanxing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China; Shanghai Collaborative Innovation Center for Biomanufacturing Technology, Shanghai 200237, China. Electronic address: qinliu@ecust.edu.cn.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism*; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D016503:Drug Delivery Systems; D005260:Female; D005453:Fluorescence; D057809:HEK293 Cells; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011108:Polymers / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D011108:Polymers; D000249:Adenosine Monophosphate
keywords: A(1)R; AMP ligand; Imaging; Nanoparticle; Tumour target