Nanoscale Ultrasound‐Switchable FRET‐Based Liposomes for Near‐Infrared Fluorescence Imaging in Optically Turbid Media

Abstract

A new approach for fluorescence imaging in optically turbid media centered on the use of nanoscale ultrasound-switchable FRET-based liposome contrast agents is reported. Liposomes containing lipophilic carbocyanine dyes as FRET pairs with emission wavelengths located in the near-infrared window are prepared. The efficacy of FRET and self-quenching for liposomes with a range of fluorophore concentrations is first calculated from measurement of the liposome emission spectra. Exposure of the liposomes to ultrasound results in changes in the detected fluorescent signal, the nature of which depends on the fluorophores used, detection wavelength, and the fluorophore concentration. Line scanning of a tube containing the contrast agents with 1 mm inner diameter buried at a depth of 1 cm in a heavily scattering tissue phantom demonstrates an improvement in image spatial resolution by a factor of 6.3 as compared with images obtained in the absence of ultrasound. Improvements are also seen in image contrast with the highest obtained being 9% for a liposome system containing FRET pairs. Overall the results obtained provide evidence of the potential the nanoscale ultrasound-switchable FRET-based liposomes studied here have for in vivo fluorescence imaging.

Recent advances in ultrasound-controlled fluorescence technology for deep tissue optical imaging

“…An NIR-UCF probe with multifunctional applications has the following properties: low toxicity, a reasonable on-to-off ratio of fluorescence intensity (I ON /I OFF ), low critical solution temperature at around normal body temperature, narrow temperature transition bandwidth, high photo- and chemical-stability, and easy functionalization by targeted molecules or peptides for achieving specific targeting of lesion tissues. Until now, three types of NIR-UCF probes have been reported: temperature-sensitive polymer NPs [ 16 ], temperature-responsive micelles [ 17 , 21 ], and thermosensitive liposomes [ 39 , 41 ]. Only ICG-loaded thermosensitive liposome and ICG-encapsulated PNIPAM NPs have been triumphantly used for in vivo NIR-UCF imaging until now; other types of temperature-sensitive polymer NPs have not been reported yet.…”

“…The results showed that the fluorescence emission intensity was increased when both the liposomes were exposed to ultrasound radiation. In 2017, Zhang et al [ 41 ] developed a nanoscale ultrasound-switchable liposome fluorescent probe for NIR fluorescence imaging in optically turbid media based on the mechanism of the fluorescence resonance energy transfer (FRET) via ultrasound irradiation means. The results indicated that this method improved the image spatial resolution by 6.3 times as compared to that of the traditional fluorescence imaging.…”

Fluorescent Phase-Changing Perfluorocarbon Nanodroplets as Activatable Near-Infrared Probes

“…Ultrasound-sensitive fluorescent agents can be synthesized in either microbubble [16,18] or nanoparticle forms [10,13,19,20]. Microbubbles expand and contract in response to incident acoustic waves.…”

A Biocompatible and Near‐Infrared Liposome for In Vivo Ultrasound‐Switchable Fluorescence Imaging

“…Biomedical imaging contributes enormously to the diagnosis of disease by providing valuable information such as disease type, location, severity, and mechanism. Fluorescence imaging is one of the major noninvasive imaging strategies, attracting immense interests with medical imaging applications . One of the advantages of fluorescence imaging is that molecular targeting and dynamic development track in real time with carefully engineered contrast agents .…”

“…Fluorescence imaging is one of the major noninvasive imaging strategies, attracting immense interests with medical imaging applications. [1][2][3][4] One of the advantages of fluorescence imaging is that molecular targeting and dynamic development track in real time with carefully engineered contrast agents. [5][6][7] Additionally, different fluorophores with distinctive emission spectra allow tagging of various biological structures, helping to achieve multicolor imaging.…”