A robust NIR fluorescence-activated probe for peroxynitrite imaging in cells and mice osteoarthritis models.

Osteoarthritis (OA) is the most common type of joint disease, which is difficult to treat, but early standardized diagnosis and treatment can effectively alleviate the pain and symptoms of patients. Therefore, it is important to construct an effective tool to assist in the early diagnosis and evaluation of the therapeutic effect of OA. In this work, a near-infrared (NIR) fluorescence-activated fluorescent probe, YB-1, was constructed for the evaluation of the diagnostic and therapeutic efficacy of OA via detection and imaging of the biomarker of ONOO- in inflammatory cells and mice osteoarthritis models. YB-1 exhibited high selectivity, high sensitivity, and a high ratio yield (I668/I0) fluorescence increasing (∼30 folds). Besides, YB-1 can be used effectively to image endogenous and exogenous ONOO- in living human chondrocytes cells (TC28a2), as well as to evaluate the effect of drug (Chrysosplenol D, CD) treatment in IL-1ß-induced inflammatory cells model. Interestingly, YB-1 was available for OONO- imaging analysis in the collagenase-induced mice OA models and assessment of the effect of CD treatment in mice OA models, with good results. Thus, the newly constructed YB-1 is a powerful molecular tool for the diagnosis and treatment of OA-related diseases.

Construction of a robust turn-on fluorescence NIR sensor for rapid detection and imaging of ONOO- in inflammatory models.

Peroxynitrite (OONO-) is closely related to the occurrence and development of health and inflammatory diseases. The physiological and pathological results of OONO- are related to the local concentration of ONOO-. Therefore, to develop of a simple, rapid and reliable OONO- detection tool is badly needed. In this work, we developed a small-molecule near-infrared (NIR) turn-on fluorescence sensor (NN1), harnessing a well-known response group phenylboronic acid response toward OONO-. It shows high detection sensitivity and yields a ratio (I658/I0) fluorescence enhancement (∼280-fold). In addition, NN1 can be effectively used to detect endogenous and exogenous ONOO- in living inflammatory cells. Notably, NN1 can be applied to OONO- imaging analysis in drug-induced inflammatory mice model with satisfactory results. Therefore, NN1 is a robust molecular biological tool, which has a good prospect in the study of ONOO- and the occurrence and development of inflammatory diseases.

A robust high selectivity fluorescence turn-on nanoprobe for peroxynitrite detection in inflammatory cells and mice.

Changed levels of intracellular peroxynitrite anion (ONOO-) are closely related to the occurrence and development of inflammation. Specific imaging of ONOO- at sites of inflammation can be of great significance not only for inflammation diagnosis but also for obtaining a deeper understanding of the role of ONOO- in inflammation. Therefore, there is an urgent need for constructing some reliable tools to study the relationship between ONOO- and inflammation in biosystems. In this work, we developed a robust high selectivity fluorescence turn-on nanoprobe (Rhb-ONOO) for inflammation-targeted imaging of ONOO-. The Rhb-ONOO was obtained by self-assembly of amphiphilic Rhb-ONOO, which was constructed by the condensation reaction of the hydrophobic, ONOO--response and deep red-emitting fluorophore (Rhb) with hydrophilic biopolymer glycol chitosan (GC). Rhb-ONOO showed rapid response towards ONOO- during 60 s, high sensitivity with 19-fold enhancement of fluorescence intensity ratio (I628/I0), and excellent selectivity towards ONOO- over other analytes as well as a good linear relationship was observed between the I628/I0 and the ONOO- concentration range 0-1 µM, with an excellent limit of detection (LOD) of 33 nM. Impressively, it was successfully employed Rhb-ONOO for ONOO- imaging in living inflammatory cells and drug-induced inflammatory mice, illustrating nanoprobe Rhb-ONOO has excellent potential for further study ONOO--related inflammatory diseases.