Thermoresponsive core cross-linked micelles for selective ratiometric fluorescent detection of Hg2+ ions

We report on the fabrication of core cross-linked (CCL) micelles possessing thermoresponsive cores and their application as sensitive and selective ratiometric Hg(2+) probes with thermo-tunable detection efficiency. Well-defined double hydrophilic block copolymer (DHBC) bearing naphthalimide-based Hg(2+)-reactive moieties (NUMA, 4), PEO-b-P(NIPAM-co-NAS-co-NUMA), was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, where PEO, NIPAM, and NAS represent poly(ethylene oxide), N-isopropylacrylamide, and N-acryloxysuccinimide. At 25 °C, PEO-b-P(NIPAM-co-NAS-co-NUMA) unimers in aqueous solution can act as ratiometric Hg(2+) probes with a detection limit of ～10.1 nM. After core cross-linking of the micellar nanoparticles formed at elevated temperatures, structurally stable CCL micelles with well-solvated PEO coronas and thermoresponsive cores embedded with Hg(2+)-reactive NUMA moieties were obtained. Upon Hg(2+) addition, the aqueous dispersion of CCL micelles exhibit a colorimetric transition from yellowish to colorless and a fluorometric emission transition from green to bright blue. Moreover, Hg(2+) detection limits of CCL micelles were considerably enhanced to 3.0 and 1.8 nM at 25 and 40 °C, when the thermoresponsive cores are at their swollen and collapsed state, respectively. The high selectivity of CCL micelles to Hg(2+) over other common cations was also demonstrated. Furthermore, in vitro studies revealed that CCL micelles can effectively enter into living cells and sensitively respond to the presence of Hg(2+) ions via the change of fluorescence emission color. This work represents the first example of DHBC-based CCL micelle acting as highly selective and sensitive ratiometric metal ion probes. The structural stability, water dispersibility, biocompatibility, and most importantly the thermo-tunable detection sensitivity of this novel type of CCL micelle-based sensing systems augur well for their future applications as multifunctional nanocarriers for drug delivery, sensing, imaging, and diagnosis.