A General and Facile Strategy to Fabricate Multifunctional Nanoprobes for Simultaneous (19)F Magnetic Resonance Imaging, Optical/Thermal Imaging, and Photothermal Therapy.

(19)F magnetic resonance imaging (MRI), due to its high sensitivity and negligible background, is anticipated to be a powerful noninvasive, sensitive, and accurate molecular imaging technique. However, the major challenge of (19)F MRI is to increase the number of (19)F atoms while maintaining the solubility and molecular mobility of the probe. Here, we successfully developed a facile and general strategy to synthesize the multifunctional (19)F MRI nanoprobes by encapsulating the hydrophobic inorganic nanoparticles (NPs) into a hybrid polymer micelle consisting of hydrolysates of 1H,1H,2H,2H-perfluorodecyltriethoxysilane (PDTES) and oleylamine-functionalized poly(succinimide) (PSIOAm). Due to their good water dispersibility, excellent molecular mobility resulting from the ultrathin coating, and high (19)F atom numbers, these nanoprobes generate a separate sharp singlet of (19)F nuclear magnetic resonance (NMR) signal (at -82.8 ppm) with half peak width of ∼28 Hz, which is highly applicable for (19)F MRI. Significantly, by varying the inorganic core from metals (Au), oxides (Fe3O4), fluorides (NaYF4:Yb(3+)/Er(3+)), and phosphates (YPO4) to semiconductors (Cu7S4 and Ag2S, ZnS:Mn(2+)) NPs, which renders the nanoprobes' multifunctional properties such as photothermal ability (Au, Cu7S4), magnetism (Fe3O4), fluorescence (ZnS:Mn(2+)), near-infrared (NIR) fluorescence (Ag2S), and upconversion (UC) luminescence. Meanwhile, the as-prepared nanoprobes possess relatively small sizes (about 50 nm), which is beneficial for long-time circulation. The proof-of-concept in vitro (19)F NMR and photothermal ablation of ZnS:Mn(2+)@PDTES/PSIOAm and Cu7S4@PDTES/PSIOAm nanoprobes further suggest that these nanoprobes hold wide potentials for multifunctional applications in biomedical fields.