Premium
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
Author(s) -
Huang Lixia,
Yan Chenggong,
Cui Danting,
Yan Yichen,
Liu Xiang,
Lu Xinwei,
Tan Xiangliang,
Lu Xiaodan,
Xu Jun,
Xu Yikai,
Liu Ruiyuan
Publication year - 2015
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201400403
Subject(s) - folate receptor , hela , chemistry , in vivo , magnetic resonance imaging , ethylene glycol , mri contrast agent , in vitro , click chemistry , cytotoxicity , internalization , biophysics , cancer research , nuclear magnetic resonance , biochemistry , receptor , gadolinium , cancer cell , cancer , combinatorial chemistry , medicine , organic chemistry , biology , physics , microbiology and biotechnology , radiology
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.