Two important challenges in the field of F magnetic resonance imaging (MRI) are the maintenance of high fluorine content without compromising imaging performance, and effective targeting of small particles to diseased tissue. To address these challenges, we have developed a series of perfluoropolyether (PFPE)-based hyperbranched (HBPFPE) nanoparticles with attached peptide aptamer as targeting ligands for specific in vivo detection of breast cancer with highF MRI sensitivity. A detailed comparison of the HBPFPE nanoparticles (NPs) with the previously reported trifluoroethyl acrylate (TFEA)-based polymers demonstrates that the mobility of fluorinated segments of the HBPFPE nanoparticles is significantly enhanced (F T > 80 ms vs 31 ms), resulting in superior MR imaging sensitivity. Selective targeting was confirmed by auto- and pair correlation analysis of fluorescence microscopy data, in vitro immunofluorescence, in vivo F MRI, ex vivo fluorescence andF NMR. The results highlight the high efficiency of aptamers for targeting and the excellent sensitivity of the PFPE moieties for F MRI. Of relevance to in vivo applications, the PFPE-based polymers exhibit much faster clearance from the body than the previously introduced perfluorocarbon emulsions ( t ∼ 20 h vs up to months). Moreover, the aptamer-conjugated NPs show significantly higher tumor-penetration, demonstrating the potential of these imaging agents for therapeutic applications. This report of the synthesis of polymeric aptamer-conjugated PFPE-based F MRI CAs with high fluorine content (∼10 wt %) demonstrates that these NPs are exciting candidates for detecting diseases with high imaging sensitivity.

Imaging agents that can be targeted to specific diseases and respond to the microenvironment of the diseased tissue are of considerable interest due to their potential in diagnosing and managing diseases. Here we report a new class of branched fluorinated glycopolymers as 19 F MRI contrast agents which respond to a reductive environment, for targeted imaging of cancer. The fluorinated glycopolymers can be readily prepared by a one-pot RAFT polymerization of glucose-and fluorine-containing monomers in the presence of a disulfide-containing crosslinking monomer. The incorporation of glucose units along the polymer chain enables these fluorinated glycopolymers to effectively target cancer cells due to interactions with the over-expressed sugar transporters present on the cell surface. In addition, the polymers exhibit an enhanced 19 F MRI signal in response to a reductive environment, one of the unique hallmarks of many cancer cells, demonstrating their potential as promising candidates for targeted imaging of cancer.

The conjugation of hydrophilic low‐fouling polymers to therapeutic molecules and particles is an effective approach to improving their aqueous stability, solubility, and pharmacokinetics. Recent concerns over the immunogenicity of poly(ethylene glycol) has highlighted the importance of identifying alternative low fouling polymers. Now, a new class of synthetic water‐soluble homo‐fluoropolymers are reported with a sulfoxide side‐chain structure. The incorporation of fluorine enables direct imaging of the homopolymer by 19F MRI, negating the need for additional synthetic steps to attach an imaging moiety. These self‐reporting fluoropolymers show outstanding imaging sensitivity and remarkable hydrophilicity, and as such are a new class of low‐fouling polymer for bioconjugation and in vivo tracking.

19F magnetic resonance imaging (19F MRI) agents capable of being activated upon interactions with cancer triggers are attracting increasing attention, although challenges still remain for precise and specific detection of cancer tissues. In this study, a novel hybrid 19F MRI agent for pH‐sensitive detection of breast cancer tissues is reported, a composite system designed by conjugating a perfluoropolyether onto the surface of manganese‐incorporated layered double hydroxide (Mn‐LDH@PFPE) nanoparticles. The 19F NMR/MRI signals from aqueous solutions of Mn‐LDH@PFPE nanoparticles are quenched at pH 7.4, but “turned on” following a reduction in pH to below 6.5. This is due to partial dissolution of Mn2+ from the Mn‐LDH nanoparticles and subsequent reduction in the effect of paramagnetic relaxation. Significantly, in vivo experiments reveal that an intense 19F MR signal can be detected only in the breast tumor tissue after intravenous injection of Mn‐LDH@PFPE nanoparticles due to such a specific activation. Thus pH‐activated Mn‐LDH@PFPE nanoparticles are a potential “smart” 19F MRI agent for precise and specific detection of cancer diseases.

19 F magnetic resonance imaging (MRI) is a powerful non-invasive imaging technique that shows tremendous potential for the diagnosis and monitoring of human diseases. Fluorinated compounds are commonly used as 19 F MRI contrast agents to develop "hot spot" imaging. To achieve high-resolution MR images, a high density of 19 F nuclei are required in the contrast agents. However, due to the inherent hydrophobicity of fluorinated moieties, aggregation of 19 F contrast agents with high fluorine content is often observed in aqueous solution, resulting in attenuated MR signal and low sensitivity, thus significantly limiting their further biological applications. Here we report the synthesis and characterization of a series of polymeric 19 F MRI contrast agents with high fluorine content by copolymerizing the well-known fluorinated monomer 2,2,2-trifluoroethyl acrylate (TFEA) with a highly water soluble monomer 2-(methylsulfinyl)ethyl acrylate (MSEA) using RAFT polymerization. We show that these polymeric contrast agents, although with high fluorine content, display remarkable imaging performance as evidenced by preferable relaxation properties and intense in vitro/vivo MRI signals, demonstrating the huge potential for eventual clinical applications such as MRI-guided disease diagnosis and therapy.

The conjugation of hydrophilic low‐fouling polymers to therapeutic molecules and particles is an effective approach to improving their aqueous stability, solubility, and pharmacokinetics. Recent concerns over the immunogenicity of poly(ethylene glycol) has highlighted the importance of identifying alternative low fouling polymers. Now, a new class of synthetic water‐soluble homo‐fluoropolymers are reported with a sulfoxide side‐chain structure. The incorporation of fluorine enables direct imaging of the homopolymer by 19F MRI, negating the need for additional synthetic steps to attach an imaging moiety. These self‐reporting fluoropolymers show outstanding imaging sensitivity and remarkable hydrophilicity, and as such are a new class of low‐fouling polymer for bioconjugation and in vivo tracking.

The conjugation of hydrophilic polymers to proteins is an effective approach to prolonging their circulation time in the bloodstream and, hence, improving their delivery to the target region of interest. In this work, we report the synthesis of protein−polymer conjugates using a highly water-soluble sulfoxide-containing polymer, poly(2-(methylsulfinyl)ethyl acrylate) (PMSEA), through a combination of "grafting-to" and "graftingfrom" methods. Oligomeric MSEA was synthesized by conventional reversible addition−fragmentation chain transfer (RAFT) polymerization and subsequently conjugated to lysozyme to produce a macromolecular chain transfer agent. This was followed by a visible lightmediated chain extension polymerization of MSEA to obtain a lysozyme−PMSEA conjugate (Lyz-PMSEA). It was found that the Lyz-PMSEA conjugate exhibited much reduced macrophage cellular uptake compared with unmodified and PEGylated lysozyme. Moreover, the Lyz-PMSEA conjugate was able to circulate longer in the bloodstream, demonstrating significantly improved pharmacokinetics demanded for pharmaceutical applications.

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