Optically Activatable Double-Drug-Loaded Perfluorocarbon Nanodroplets for On-Demand Image-Guided Drug Delivery

Spatarelu, Catalina-Paula; Namen, Austin Van; Luke, Geoffrey P.

doi:10.1021/acsanm.1c01303

Cited by 10 publications

(4 citation statements)

References 58 publications

(91 reference statements)

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“…An additional benefit of using a lower-boiling-point core is the ability to release cargo on demand. Therefore, the nanodroplets could be used for molecularly targeted drug delivery with ultrasound image guidance [18,36,37].…”

Section: Discussionmentioning

confidence: 99%

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EGFR-Targeted Perfluorohexane Nanodroplets for Molecular Ultrasound Imaging

et al. 2022

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Perfluorocarbon nanodroplets offer an alternative to gaseous microbubbles as contrast agents for ultrasound imaging. They can be acoustically activated to induce a liquid-to-gas phase transition and provide contrast in ultrasound images. In this study, we demonstrate a new strategy to synthesize antibody-conjugated perfluorohexane nanodroplet (PFHnD-Ab) ultrasound contrast agents that target cells overexpressing the epidermal growth factor receptor (EGFR). The perfluorohexane nanodroplets (PFHnD) containing a lipophilic DiD fluorescent dye were synthesized using a phospholipid shell. Antibodies were conjugated to the surface through a hydrazide-aldehyde reaction. Cellular binding was confirmed using fluorescence microscopy; the DiD fluorescence signal of the PFHnD-Ab was 5.63× and 6× greater than the fluorescence signal in the case of non-targeted PFHnDs and the EGFR blocking control, respectively. Cells were imaged in tissue-mimicking phantoms using a custom ultrasound imaging setup consisting of a high-intensity focused ultrasound transducer and linear array imaging transducer. Cells with conjugated PFHnD-Abs exhibited a significantly higher (p < 0.001) increase in ultrasound amplitude compared to cells with non-targeted PFHnDs and cells exposed to free antibody before the addition of PFHnD-Abs. The developed nanodroplets show potential to augment the use of ultrasound in molecular imaging cancer diagnostics.

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Section: Discussionmentioning

confidence: 99%

“…Thus, the higher-boiling-point core yields the benefit of improved stability and controllable contrast. The phase change dynamics of the PFCnDs have led to their use in a variety of imaging and therapeutic applications [15,[17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

EGFR-Targeted Perfluorohexane Nanodroplets for Molecular Ultrasound Imaging

et al. 2022

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“…For example, PFCnDs can be surface-modified for molecular targeting of cancer cells [49], and the associated imaging contrast can then be specific to the region of interest, potentially providing localized contrast, and thus, improving diagnostic capabilities. Moreover, image-guided delivery of therapeutics using PFCnDs recently showed that PFCnDs have a capacity for simultaneous drug delivery and ultrasound monitoring, indicating that localized treatment and imaging of cancer with PFCnDs may be feasible in the future [50]. Furthermore, PFCnDs can be incorporated into other medical imaging modalities, including magnetic resonance imaging (MRI) as a multimodal agent [51].…”

Section: Discussionmentioning

confidence: 99%

Ultrasound and Photoacoustic Imaging of Laser-Activated Phase-Change Perfluorocarbon Nanodroplets

Yoon

2021

Photonics

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Laser-activated perfluorocarbon nanodroplets (PFCnDs) are emerging phase-change contrast agents that showed promising potential in ultrasound and photoacoustic (US/PA) imaging. Unlike monophase gaseous microbubbles, PFCnDs shift their state from liquid to gas via optical activation and can provide high US/PA contrast on demand. Depending on the choice of perfluorocarbon core, the vaporization and condensation dynamics of the PFCnDs are controllable. Therefore, these configurable properties of activation and deactivation of PFCnDs are employed to enable various imaging approaches, including contrast-enhanced imaging and super-resolution imaging. In addition, synchronous application of both acoustic and optical pulses showed a promising outcome vaporizing PFCnDs with lower activation thresholds. Furthermore, due to their sub-micrometer size, PFCnDs can be used for molecular imaging of extravascular tissue. PFCnDs can also be an effective therapeutic tool. As PFCnDs can carry therapeutic drugs or other particles, they can be used for drug delivery, as well as photothermal and photodynamic therapies. Blood barrier opening for neurological applications was recently demonstrated with optically-triggered PFCnDs. This paper specifically focuses on the activation and deactivation properties of laser-activated PFCnDs and associated US/PA imaging approaches, and briefly discusses their theranostic potential and future directions.

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“…In biomedical applications, the submicron droplets with properly coated surfaces are able to escape from the detection of the immune system while moving in blood vessels [ 4 ]. They can be used as contrast agents in cancer tissues for imaging diagnosis, and as carriers for drug delivery [ 5 ]. In the energy industry for the enhanced oil recovery, especially in rocks with characteristic pore size at submicron scale, submicron droplets are used as carriers of surfactants that help to emulsify and recover oil [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Microfluidic Methods for Generation of Submicron Droplets: A Review

Huang

Xie

2023

Micromachines

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Submicron droplets are ubiquitous in nature and widely applied in fields such as biomedical diagnosis and therapy, oil recovery and energy conversion, among others. The submicron droplets are kinetically stable, their submicron size endows them with good mobility in highly constricted pathways, and the high surface-to-volume ratio allows effective loading of chemical components at the interface and good heat transfer performance. Conventional generation technology of submicron droplets in bulk involves high energy input, or relies on chemical energy released from the system. Microfluidic methods are widely used to generate highly monodispersed micron-sized or bigger droplets, while downsizing to the order of 100 nm was thought to be challenging because of sophisticated nanofabrication. In this review, we summarize the microfluidic methods that are promising for the generation of submicron droplets, with an emphasize on the device fabrication, operational condition, and resultant droplet size. Microfluidics offer a relatively energy-efficient and versatile tool for the generation of highly monodisperse submicron droplets.

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Optically Activatable Double-Drug-Loaded Perfluorocarbon Nanodroplets for On-Demand Image-Guided Drug Delivery

Cited by 10 publications

References 58 publications

EGFR-Targeted Perfluorohexane Nanodroplets for Molecular Ultrasound Imaging

EGFR-Targeted Perfluorohexane Nanodroplets for Molecular Ultrasound Imaging

Ultrasound and Photoacoustic Imaging of Laser-Activated Phase-Change Perfluorocarbon Nanodroplets

Microfluidic Methods for Generation of Submicron Droplets: A Review

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