Abstract
Nanoparticles have extensively been used for cancer therapy and imaging (i.e., theranostics) using various imaging modalities. Due to their physical and chemical properties (e.g., absorption, fluorescence, and magnetic properties) they have been used for image guided therapy for cancer treatment monitoring. There are various limitations that make many theranostic agents unable to be used for the extended periods of time required for enhancing theranostic capabilities. Some of these are due to inherent characteristics (e.g., change and/or breakdown of structure) present upon continuous irradiation and others are due to environmental (i.e., physiological) conditions that can lead to physical instability (i.e., in terms of size) affecting the amount of particles that can accumulate at the target site and the overall contrast that can be achieved. In this study, perfluorohexane (PFH) nanoemulsions (NEs) were synthesized with silica coated gold nanoparticles (PFH-NEs-scAuNPs) in order to give both stable and enhanced signals for cancer imaging by increasing vaporization of the emulsions into bubbles through the process of optical droplet vaporization (ODV). The resulting perfluorohexane bubbles could be imaged using nonlinear ultrasound (NL US) which significantly increases the signal to noise ratio due to the nonlinear scattering properties of oscillating bubbles. The NL US signals from PFH bubbles were found to be more stable compared to conventional bubbles used for contrast imaging. In addition, the vaporization of PFH NEs into bubbles was shown to cause significant cancer cell death reflecting the theranostic capabilities of the formed PFH bubbles. Since cell death is initiated with laser excitation of PFH-NEs-scAuNPs, these nanoparticles can specifically target cancer cells once they have accumulated at the tumor region. Due to the type of theranostic agent and imaging modality used, the PFH-NEs-scAuNPs can be used to provide higher specificity compared to other agents for locating the tumor region by minimizing tissue specific signals while at the same time being used to treat cancer.
Highlights
Nanotechnology is a very fast growing and interdisciplinary eld bringing together knowledge from chemistry, biology, physics and engineering
A signi cant number of highly scattering nanoparticles from both un uorinated and uorinated samples were localized at the membranes of cells (Fig. 3a and b), with the formation of signi cant amount of PFH bubbles seen in vitro a er bright eld illumination (ESI Fig. S4a and b†). These results suggest the potential of PFH-NEs-scAuNPs for contrast enhanced ultrasound (CEUS) imaging, by their ability to strongly attach to the membranes of cancer cells where the CEUS signals from bubbles can be used to speci cally image tumors
PFH-NEs-scAuNPs can be used to increase both nonlinear ultrasound signals and cell death due to the reduction of the vaporization threshold and energy required for converting PFHNEs into bubbles
Summary
Nanotechnology is a very fast growing and interdisciplinary eld bringing together knowledge from chemistry, biology, physics and engineering. Compared to other imaging modalities (i.e., uorescence and optical coherence tomography (OCT)), PA imaging can provide greater spatial resolution and deeper tissue penetration due to detection of ultrasonic signals, which attenuate less compared to visible electromagnetic waves.[20] In our previous work we synthesized per uorohexane nanoemulsions (PFH-NEs) that were able to give photoacoustic signals through the intrinsic near-infrared absorption properties of the uorosurfactant shell of particles.[21] The photoacoustic signals detected were from the vaporization of PFH-NEs into PFH bubbles due to conversion of the volatile PFH liquid into gas through the process of optical droplet vaporization (ODV).[22] Coupling PFH-NEs with silica coated gold nanoparticles (scAuNPs) was shown to further increase PA signals in tissuemimicking phantoms[23] due to the enhanced absorption from scAuNPs surrounding the NEs. even with the ability to provide strong acoustic signals, when using photoacoustic imaging in vivo, the background signal from blood and other tissue chromophores can reduce the contrast between tissues in which PFH-NEs-scAuNPs have accumulated and the surrounding tissues, even a er spectral unmixing is applied. An approach with a greater target-to-background ratio is needed
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