Novel turn-on fluorescent biosensors for selective detection of cellular Fe3+ in lysosomes: Thiophene as a selectivity-tuning handle for Fe3+ sensors

• Published in: Dyes and pigments Vol. 169; pp. 51 - 59
• Main Authors: Lim, Bumhee, Baek, Byungyeob, Jang, Kyungkuk, Lee, Na Keum, Lee, Ji Hye, Lee, Yeongcheol, Kim, Jinwoo, Kang, San Won, Park, Jaehyun, Kim, Suzi, Kang, Nae-Won, Hong, Suckchang, Kim, Dae-Duk, Kim, Ikyon, Hwang, Hyonseok, Lee, Jeeyeon
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.10.2019
• ISSN: 0143-7208; 1873-3743
• DOI: 10.1016/j.dyepig.2019.05.008

Iron-selective turn-on sensors are indispensable tools for understanding iron-related cell death processes and human diseases. In this study, we report a novel class of fluorescent sensors derived from an indolizino[3,2-c]quinoline scaffold that exhibit high selectivity for Fe3+ over other biologically abundant cations in cells, including Fe2+, Al3+, Zn2+, and Mn2+. IQ18 works as a ratiometric sensor with a Kd value of 7.1 × 10 −7 M and a detection limit of 5.2 nM in ethanol, whereas IQ44 displays fluorescence enhancement upon binding with Fe3+ in both ethanol and water. In aqueous solution, IQ44 exists as 150-nm nanoparticles. The suppressed fluorescent emission of IQ44 nanoparticles in water is switched on in response to Fe3+, working as a turn-on nanoparticle sensor. Structure-property relationship analysis with IQ derivatives revealed that the thiophene ring confers selectivity for Fe3+. By installing thiophene in IQ44 as a selectivity-tuning handle, fluorescence in the presence of Fe3+ resulting from restriction of intramolecular rotation (RIR) and increased torsion angle induced by iron demonstrated that IQ44 is specifically localized in lysosomes, where it recognizes cellular Fe3+ in live cells, as determined using confocal microscopy. In addition, the increased fluorescent puncta of IQ44 in the presence of Fe3+ colocalized well with the RFP-tagged LC3 proteins (pmRFP-LC3), enabling the detection of the autophagy process. •We developed novel indolizino[3,2-c]quinoline (IQ)-based fluorescent sensors (IQ18 and IQ44) for Fe3+.•IQ18 works as a ratiometric sensor, whereas IQ44 works as a ∼150 nm turn-on nanoparticle sensor for Fe3+ in water.•IQ44 is specifically localized in lysosomes, where it recognizes cellular Fe3+ in live cells.