Intratumoral Glutathione Activatable Nanoprobes for Fluorescence and ¹⁹F Magnetic Resonance Turn-On Imaging

Abstract

Tumor microenvironment turn-on nanoprobes that could specifically detect the occurrence of diseases possess great potential in early diagnosis. Here, a GSH activated nanoprobe was designed for fluorescence and 19 F magnetic resonance (MR) dualmodal turn-on imaging of tumors. Specifically, fluorescence AgInS 2 quantum dots (QDs for fluorescence imaging) were coencapsulated with perfluoro-15-crown-5-ether (P 19 FCE for 19 F MRI) by amphiphilic polymers and further coated with in situ formed manganese dioxide (MnO 2 ) nanoshells, which served as efficient fluorescence and 19 F MR quenchers due to energy transfer and paramagnetic relaxation effects, respectively. The overexpressed GSH in tumors would decompose the MnO 2 nanoshells, resulting in remarkable enhancement of both fluorescence and 19 F MRI signals of the nanoprobes, accordingly lighting up the tumor site.

19F MRI Probes for Multimodal Imaging**

“…Standard NIR fluorescent dyes such as indocyanine green (ICG), [53,54] Cy5.5, [55] ZnS [57] and AgInS 2 [56] quantum dots have been used for encapsulation without prior chemical modifications. The exception was Cy5.5 conjugated to a symmetrical dendron with 27 identical fluorine nuclei (Figure 16) as a single bifunctional 19 F/NIR agent [55] .…”

“…An alternative approach is to separate a fluorous phase from the aqueous phase using a hydrophilic shell. Hydrophilic polymers such as poly(lactic-coglycolic acid) (PLGA) [52][53][54][55] and polysuccinimides [23,56] are wellsuited for this purpose as they can entrap hydrophobic compounds while retaining their native solubility. The synthesis proceeds by emulsification of the desired formulation with the polymer in an organic solvent and subsequent separation of [47,48] Reproduced with permission.…”

“…The resulting particles are customizable in terms of their content ( 19 F imaging agent, fluorescent dye, drug) and size (typically 10-200 nm) as well as coating. Perfluorocarbons such as perfluoro-15-crown-5ether (PFCE), [53,56,57] perfluoro-octyl bromide (PFOB), [54] 1H,1H,2H,2H-perfluorodecyltriethoxysilane (PDTES) [23] or a fluorinated dendron [55] have been proposed as a 19 F MRI signal source. Srinivas et al investigated several fluororganic compounds and demonstrated the impact of the number of NMR peaks on the quality of MRI images (Figure 15).…”

“…Srinivas et al investigated several fluororganic compounds and demonstrated the impact of the number of NMR peaks on the quality of MRI images (Figure 15). [52] Standard NIR fluorescent dyes such as indocyanine green (ICG), [53,54] Cy5.5, [55] ZnS [57] and AgInS 2 [56] quantum dots have been used for encapsulation without prior chemical modifications. The exception was Cy5.5 conjugated to a symmetrical dendron with 27 identical fluorine nuclei (Figure 16) as a single bifunctional 19 F/NIR agent.…”

“…[54] The polymeric capsules can be used as responsive agents. To achieve the off/on feature, an additional MnO 2 [56] or manganese oleate [57] coating was proposed by Leyu Wang's team. In their designs 19 F NMR and fluorescence signals were quenched by the Mn(II) nanoshells either due to the PRE effect or the energy transfer process, respectively.…”