No abstract

Photothermal therapy (PTT), as a minimally invasive and highly effective cancer treatment approach, has received widespread attention in recent years. Tremendous effort has been devoted to explore various types of photothermal agents with high near-infrared (NIR) absorbance for PTT cancer treatment. Despite many exciting progresses in the area, effective yet safe photothermal agents with good biocompatibility and biodegradability are still highly desired. In this work, a new organic PTT agent based on polyethylene glycol (PEG) coated micelle nanoparticles encapsulating a heptamethine indocyanine dye IR825 is developed, showing a strong NIR absorption band and a rather low quantum yield, for in vivo photothermal treatment of cancer. It is found that the IR825-PEG nanoparticles show ultra-high in vivo tumor uptake after intravenous injection, and appear to be an excellent PTT agent for tumor ablation under a low-power laser irradiation, without rendering any appreciable toxicity to the treated animals. Compared with inorganic nanomaterials and conjugated polymers being explored in PTT, the NIR-absorbing micelle nanoparticles presented here may have the least safety concern while showing excellent treatment effi cacy, and thus may be a new photothermal agent potentially useful in clinical applications.

The applications of fluorinated molecules in bioengineering and nanotechnology are expanding rapidly with the controlled introduction of fluorine being broadly studied due to the unique properties of C−F bonds. This review will focus on the design and utility of C−F containing materials in imaging, therapeutics, and environmental applications with a central theme being the importance of controlling fluorine−fluorine interactions and understanding how such interactions impact biological behavior. Low natural abundance of fluorine is shown to provide sensitivity and background advantages for imaging and detection of a variety of diseases with 19 F magnetic resonance imaging, 18 F positron emission tomography and ultrasound discussed as illustrative examples. The presence of C−F bonds can also be used to tailor membrane permeability and pharmacokinetic properties of drugs and delivery agents for enhanced cell uptake and therapeutics. A key message of this review is that while the promise of C−F containing materials is significant, a subset of highly fluorinated compounds such as per-and polyfluoroalkyl substances (PFAS), have been identified as posing a potential risk to human health. The unique properties of the C−F bond and the significant potential for fluorine−fluorine interactions in PFAS structures necessitate the development of new strategies for facile and efficient environmental removal and remediation. Recent progress in the development of fluorine-containing compounds as molecular imaging and therapeutic agents will be reviewed and their design features contrasted with environmental and health risks for PFAS systems. Finally, present challenges and future directions in the exploitation of the biological aspects of fluorinated systems will be described.

19 F magnetic resonance imaging (MRI) is a powerful noninvasive imaging technique with demonstrated potential for the detection of important diseases. The major challenge in the design of 19 F MRI agents is signal attenuation caused by the reduced solubility and segmental mobility of probes with high numbers of fluorine atoms. Careful choice of the fluorinated moiety is required to maintain image quality at the fluorine contents required for high imaging sensitivity. Here we report the synthesis of perfluoropolyether (PFPE) end-functionalized homopolymers of oligo(ethylene glycol) methyl ether acrylate (poly(OEGA) m -PFPE) as highly sensitive 19 F MRI contrast agents (CAs). The structural characteristics, conformation and aggregation behavior, 19 F NMR relaxation properties, and 19 F MR imaging were studied in detail. Dynamic light scattering and molecular dynamics (MD) simulations were conducted and demonstrated that poly(OEGA) m -PFPE with the longest poly(OEGA) m segments (m = 20) undergoes single-chain folding in water while poly(OEGA) 10 -PFPE and poly(OEGA) 4 -PFPE with shorter OEGA segments experience multiple-chain aggregation. Long 19 F T 2 relaxation times were measured for all poly(OEGA) m -PFPE polymers in PBS and in the presence of serum (>80 ms), and no obvious decrease in 19 F T 2 was observed with increasing fluorine content up to ∼30 wt %. Moreover, the signal-to-noise ratio increased linearly with increasing concentration of fluorine, indicating that the PFPE-based polymers can be applied as quantitative tracers. Furthermore, we investigated the in vivo behavior, in particular their biodistribution, of the polymers with different aggregation properties. Control over the balance of hydrophobicity and hydrophilicity allows manipulation of the aggregation state, and this leads to different circulation behavior in a murine model. This first report of the synthesis of polymeric PFPE-based 19 F MRI CAs demonstrates that these polymers are an exciting new class of 19 F MRI CAs with extremely high fluorine content and outstanding imaging sensitivity.