Design of Thermoresponsive Polyamine Cross-Linked Perfluoropolyether Hydrogels for Imaging and Delivery Applications

Abstract

Perfluorocarbons are versatile compounds with applications in 19 F magnetic resonance imaging (MRI) and chemical conjugation to drugs and pH sensors. We present a novel thermoresponsive perfluorocarbon emulsion hydrogel that can be detected by 19 F MRI. The developed hydrogel contains perfluoro(polyethylene glycol dimethyl ether) (PFPE) emulsion droplets that are stabilized through ionic cross-linking with polyethylenimine (PEI). Specifically, PFPE ester undergoes hydrolysis upon contact with aqueous PEI solution, resulting in an ionic bond between the PFPE acid and charged PEI amino groups. Due to the ionic nature of the PFPE/PEI bond, potassium buffer is required to preserve the hydrogel's pH and rheological and emulsion droplet stability. The presence of the surface cross-linked PFPE droplets does not affect the hydrogel's rheological behavior, drug loading, or drug release, and the hydrogel is nontoxic. We propose that the presented hydrogel can be adapted to a broad range of biomedical imaging and delivery applications.

19F MRI Nanotheranostics for Cancer Management: Progress and Prospects

“…PFPEs, long‐chain polyethers in which all hydrogens have been replaced by fluorine atoms, are outstanding representatives of linear polymers. This series of polymers has similar physicochemical properties, that is, large molecular weight (>1700 Da), high fluorine content (approximately 40 19 F atoms per molecule), strongly hydrophobic and mildly lipophobic properties, high boiling points, low surface tension, very similar spectral properties (a main peak at −92 ppm (−CF 2 O) and other small peaks due to the terminal fluorinated groups), as well as favorable relaxivity (T 1 and T 2 ) [47] . In recent years, PFPEs and their modifiers have been formulated into various tracers and used in 19 F MRI of tumors.…”

Nanotechnology as a Versatile Tool for 19F-MRI Agent’s Formulation: A Glimpse into the Use of Perfluorinated and Fluorinated Compounds in Nanoparticles

“…The same group had used a slightly modified hydrogel for increasing its ability to load different payloads (fluorescent dyes, pH sensors, chelators, drugs, and antibodies) and therefore adapt the hydrogel for a broad range of biomedical imaging and delivery applications. PFPE nanoemulsions were crosslinked with polyethylenimine to form hydrogels hence ridding the necessity of any energy utilizing the emulsification step [252].…”

Shortwave Infrared Fluorofluorophores for Multicolor In Vivo Imaging**

“…They have since been used as a diagnostic as well as for an expanded scope of oxygen delivery applications [34] . Additional efforts harnessing the orthogonal nature of the PFCs for drug or biomolecule delivery are underway by our group and others [35–37] . Our previous work has probed the effect of the surface chemistry of PFC nanoemulsions in cell culture using visible fluorofluorophores [38] .…”

“…[34] Additional efforts harnessing the orthogonal nature of the PFCs for drug or biomolecule delivery are underway by our group and others. [35][36][37] Our previous work has probed the effect of the surface chemistry of PFC nanoemulsions in cell culture using visible fluorofluorophores. [38] However, we had been unable to perform analogous studies in mice due to the lack of fluorofluorophores available for imaging through tissue.…”