**Cationic Fluorescent Nanogel Thermometers based on Thermoresponsive Poly(***N***-isopropylacrylamide) and Environment-Sensitive Benzofurazan**

#### **Teruyuki Hayashi 1, Kyoko Kawamoto 2, Noriko Inada 3 and Seiichi Uchiyama 2,\***


Received: 21 June 2019; Accepted: 29 July 2019; Published: 4 August 2019

**Abstract:** Cationic nanogels of *N*-isopropylacrylamide (NIPAM), including NIPAM-based cationic fluorescent nanogel thermometers, were synthesized with a cationic radical initiator previously developed in our laboratory. These cationic nanogels were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential measurements and fluorescence spectroscopy, as summarized in the temperature-dependent fluorescence response based on the structural change in polyNIPAM units in aqueous solutions. Cellular experiments using HeLa (human epithelial carcinoma) cells demonstrated that NIPAM-based cationic fluorescent nanogel thermometers can spontaneously enter the cells under mild conditions (at 25 ◦C for 20 min) and can show significant fluorescence enhancement without cytotoxicity with increasing culture medium temperature. The combination of the ability to enter cells and non-cytotoxicity is the most important advantage of cationic fluorescent nanogel thermometers compared with other types of fluorescent polymeric thermometers, i.e., anionic nanogel thermometers and cationic/anionic linear polymeric thermometers.

**Keywords:** fluorescence; imaging; nanogel; temperature; thermometer; thermometry
