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A Fluorinated Ionic Liquid-Based Activatable 19F MRI Platform Detects Biological Targets

ABSTRACT: SUMMARY 19F magnetic resonance imaging (19F MRI) is a promising technique for in vivo molecular imaging and clinical diagnosis, benefiting from its negligible background and unlimited tissue penetration depth. However, the development of 19F probes with good water solubility and versatile functions for bioresponsive and practical applications remains a challenge. Here, we report fluorinated ion liquids (ILs) as a new type of fluorine agents and build a fluorinated ionic liquid-based activatable 19F MRI platform (FILAMP), which relies on the phase transition of ILs. Upon exposure to environmental stimulation, coating polymer dissolves or degrades to release the fluorinated ILs payload, which rapidly enhances 19F signal. This “turn-on” response is verified by the successful detection of biological targets (for example, dysregulated pH and MMP overexpression) at the cellular level and in mice, demonstrating the potential of FILAMP as a robust activatable 19F probe for diagnosis and monitoring of biological and pathological processes. Graphical Abstract Fluorinated ion liquids (ILs) act as a new type of fluorine agents to build a fluorinated ionic liquid-based activatable 19F MRI platform (FILAMP). Upon biological stimulation, the coating polymer dissolves or degrades to release the payload, which rapidly enhances the 19F signals. This “turn-on” response is verified by successful detection of biological targets in vitro and in vivo. In summary, FILAMP can serve as a type of activatable 19F probes for diagnosis and monitoring of biological and pathological processes.

SUBMITTER: Zhu X

PROVIDER: S-EPMC8171808 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThere is a need to replace petroleum-derived with sustainable feedstocks for chemical production. Certain biomass feedstocks can meet this need as abundant, diverse, and renewable resources. Specific ionic liquids (ILs) can play a role in this process as promising candidates for chemical pretreatment and deconstruction of plant-based biomass feedstocks as they efficiently release carbohydrates which can be fermented. However, the most efficient pretreatment ILs are highly toxic to biological systems, such as microbial fermentations, and hinder subsequent bioprocessing of fermentative sugars obtained from IL-treated biomass.MethodsTo generate strains capable of tolerating residual ILs present in treated feedstocks, a tolerance adaptive laboratory evolution (TALE) approach was developed and utilized to improve growth of two different Escherichia coli strains, DH1 and K-12 MG1655, in the presence of two different ionic liquids, 1-ethyl-3-methylimidazolium acetate ([C2C1Im][OAc]) and 1-butyl-3-methylimidazolium chloride ([C4C1Im]Cl). For multiple parallel replicate populations of E. coli, cells were repeatedly passed to select for improved fitness over the course of approximately 40 days. Clonal isolates were screened and the best performing isolates were subjected to whole genome sequencing.ResultsThe most prevalent mutations in tolerant clones occurred in transport processes related to the functions of mdtJI, a multidrug efflux pump, and yhdP, an uncharacterized transporter. Additional mutations were enriched in processes such as transcriptional regulation and nucleotide biosynthesis. Finally, the best-performing strains were compared to previously characterized tolerant strains and showed superior performance in tolerance of different IL and media combinations (i.e., cross tolerance) with robust growth at 8.5% (w/v) and detectable growth up to 11.9% (w/v) [C2C1Im][OAc].ConclusionThe generated strains thus represent the best performing platform strains available for bioproduction utilizing IL-treated renewable substrates, and the TALE method was highly successful in overcoming the general issue of substrate toxicity and has great promise for use in tolerance engineering.

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A Fluorinated Ionic Liquid-Based Activatable 19F MRI Platform Detects Biological Targets

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