title: Organic Radical Contrast Agents Based on Polyacetylenes Containing 2,2,6,6-Tetramethylpiperidine 1-Oxyl (TEMPO): Targeted Magnetic Resonance (MR)/Optical Bimodal Imaging of Folate Receptor Expressing HeLa Tumors in Vitro and in Vivo(a).
abstract: Nitroxides have great potential as magnetic resonance imaging (MRI) contrast agents for tumor detection. Polyacetylenes(PAs) containing 2,2,6,6-tetramethyl-piperidine oxyl (TEMPO) and poly(ethylene glycol) were synthesized via metathesis polymerization of the corresponding substituted acetylenes to be used for targeted bimodal MRI /optical imaging of tumors. The poly(ethylene glycol) in the polyacetylenes enables covalent conjugation of carboxyl fluorescein and folic acid (FA) with hydroxyl groups to develop targeted multifunctional organic radical contrast agents (ORCAs). In vitro studies confirm the excellent binding specificity and subsequent enhanced cellular internalization of the targeted ORCAs (PA-TEMPO-FI-FA) without cytotoxicity. In vivo T1-weighted MRI demonstrates the active tumor targeting ability of PA-TEMPO-FI-FA to generate specific contrast enhancement in mice bearing HeLa tumors. Moreover, longitudinal optical imaging displays high tumor accumulation after 1 h post-injection of PA-TEMPO-FI-FA. These results indicate that multifunctional ORCAs may provide a tumor-targeted delivery platform for further molecular imaging guided cancer therapy.
authors: Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.|Department of Radiology, Guangdong Provincial Traditional Chinese Medical Hospital, Guangzhou, 510120, China.
authors: Lixia
authors: L
authors: Huang
authors: Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors: Chenggong
authors: C
authors: Yan
authors: Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors: Danting
authors: D
authors: Cui
authors: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
authors: Yichen
authors: Y
authors: Yan
authors: Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors: Xiang
authors: X
authors: Liu
authors: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
authors: Xinwei
authors: X
authors: Lu
authors: Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors: Xiangliang
authors: X
authors: Tan
authors: Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors: Xiaodan
authors: X
authors: Lu
authors: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors: Jun
authors: J
authors: Xu
authors: Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. yikaixu917@gmail.com.
authors: Yikai
authors: Y
authors: Xu
authors: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. ruiyliu@smu.edu.cn.
authors: Ruiyuan
authors: R
authors: Liu
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D058973:Folate Receptors, GPI-Anchored / Q000096:biosynthesis*; D006367:HeLa Cells; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D057054:Molecular Imaging; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D011859:Radiography
chemical_list: D003287:Contrast Media; D003497:Cyclic N-Oxides; D058973:Folate Receptors, GPI-Anchored; D009363:Neoplasm Proteins; C003959:TEMPO
keywords: MRI; contrast agent; folic acid; optical imaging; organic radicals