Laser-activated perfluorocarbon nanodroplets: a new tool for blood brain barrier opening

Hallam, Kristina A.; Donnelly, Eleanor; Karpiouk, Andrei; Hartman, Robin; Emelianov, Stanislav

doi:10.1364/boe.9.004527

Cited by 21 publications

(24 citation statements)

References 35 publications

(73 reference statements)

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“…All animal studies were conducted under the protocol approved by the Institutional Animal Care and Use Committee at Georgia Institute of Technology. Animal studies were performed as described previously [27]. Briefly, an injection of sustained released buprenorphine (IP, 0.8 mg/kg) was administered to each animal (Balb/c mouse, Jax), prior to anesthesia.…”

Section: In Vivo Laser-activated Pfhnd Induced Blood Brain Barrier Opmentioning

confidence: 99%

“…The sixth group of animals acted as a control group, with no laser irradiation or a co-injection. Other controls of co-injection only or laser irradiation only have been performed previously and showed no BBB opening effect, so the control here serves a baseline for the experimental groups [27]. After laser irradiation, mice were allowed to recover, with no gross behavioral damage observed.…”

Section: In Vivo Laser-activated Pfhnd Induced Blood Brain Barrier Opmentioning

confidence: 99%

“…Recently, perfluorocarbon nanodroplets (PFCnDs), a descendant of microbubbles, have been investigated as a means to transiently open the BBB [25][26][27]. PFCnDs are a phasechange nanoagent capable of changing from liquid nanodroplet to gas microbubble when activated via acoustic or electromagnetic energy [28][29][30].…”

Section: Introductionmentioning

confidence: 99%

“…Phase-change of the PFCnD occurs due to the localized heating and photoacoustic pressure wave that result from the optical trigger-laser interaction [29]. For laser-activated PFCnD induced BBB opening, we investigated perfluorohexane nanodroplets (PFHnDs) [27]. PFHnDs are attractive for use in BBB opening due to their ability to undergo repeated phase-change from liquid to gas [31][32][33][34], creating an oscillatory-like behavior and allowing laser-activated PFHnDs multiple opportunities to interact with the BBB and enable opening.…”

Section: Introductionmentioning

confidence: 99%

“…Further, PFCnDs are capable of carrying cargo within the droplet or on the shell, making them attractive as controlled release delivery vehicles [40]. Their nanometer size also makes PFCnDs capable of extravasation across barriers such as leaky vasculature within a tumor or an opened BBB [27,[40][41][42]. As a result, the versatile nature of PFCnDs shows their potential to be utilized in a wide variety of applications including the central nervous system.…”

Section: Introductionmentioning

confidence: 99%

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Toward optimization of blood brain barrier opening induced by laser-activated perfluorocarbon nanodroplets

Hallam¹,

Emelianov²

2019

Biomed. Opt. Express

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The blood brain barrier (BBB), a component of the brain's natural defense system, is often a roadblock for the monitoring and treatment of neurological disorders. Recently, we introduced a technique to open the blood brain barrier through the use of laser-activated perfluorohexane nanodroplets (PFHnDs), a phase-change nanoagent that undergoes repeated vaporization and recondensation when excited by a pulsed laser. Laser-activated PFHnDs were shown to enable noninvasive and localized opening of the BBB, allowing extravasation of various sized agents into the brain tissue. In this current work, the laser-activated PFHnDinduced BBB opening is further explored. In particular, laser fluence and the number of laser pulses used for the PFHnD-induced BBB opening are examined and evaluated both qualitatively and quantitatively to determine the effect of these parameters on BBB opening. The results of these studies show trends between increased laser fluence and an increased BBB opening as well as between an increased number of laser pulses and an increased BBB opening, however, with limitations on the extent of the BBB opening after a certain number of pulses. Overall, the results of these studies serve as a guideline to choosing suitable laser parameters for safe and effective BBB opening.

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Section: In Vivo Laser-activated Pfhnd Induced Blood Brain Barrier Opmentioning

confidence: 99%

Section: In Vivo Laser-activated Pfhnd Induced Blood Brain Barrier Opmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Toward optimization of blood brain barrier opening induced by laser-activated perfluorocarbon nanodroplets

Hallam¹,

Emelianov²

2019

Biomed. Opt. Express

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Effect of perfluorocarbon composition on activation of phase‐changing ultrasound contrast agents

et al. 2022

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Background: While microbubble contrast agents (MCAs) are commonly used in ultrasound (US), they are inherently limited to vascular targets due to their size. Alternatively, phase-changing nanodroplet contrast agents (PNCAs) can be delivered as nanoscale agents (i.e., small enough to extravasate), but when exposed to a US field of sufficient mechanical index (MI), they convert to MCAs, which can be visualized with high contrast using nonlinear US. Purpose: To investigate the effect of perfluorocarbon (PFC) core composition and presence of cholesterol in particle coatings on stability and image contrast generated from acoustic activation of PNCAs using high-frequency US suitable for clinical imaging. Methods: PNCAs with varied core compositions (i.e., mixtures of perfluoropentane [C5] and/or perfluorohexane [C6]) and two coating formulations (i.e., with and without cholesterol) were characterized and investigated for thermal/temporal stability and postactivation, nonlinear US contrast in phantom and in vivo environments. Through hydrophone measurements and nonlinear numerical modeling, MI was estimated for pulse sequences used for PNCA activation. Results: All PNCA compositions were characterized to have similar diameters (249-267 nm) and polydispersity (0.151-0.185) following fabrication. While PNCAs with majority C5 core composition showed higher levels of spontaneous signal (i.e., not due to US activation) in phantoms than C6-majority PNCAs, all compositions were stable during imaging experiments. When activating PNCAs with a 12.3-MHz US pulse (MI = 1.1), C6-core particles with cholesterol-free coatings (i.e., CF-C6-100 particles) generated a median contrast of 3.1, which was significantly higher (p < 0.001) than other formulations. Further, CF-C6-100 particles were activated in a murine model, generating US contrast ≥3.4. Conclusion: C6-core PNCAs can provide high-contrast US imaging with minimal nonspecific activation in phantom and in vivo environments.

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Use of Physical Approaches for Systemic Drug Delivery

Vadlapatla

Wang

Kumar

et al. 2020

Healthy Ageing and Longevity

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Laser-activated perfluorocarbon nanodroplets: a new tool for blood brain barrier opening

Cited by 21 publications

References 35 publications

Toward optimization of blood brain barrier opening induced by laser-activated perfluorocarbon nanodroplets

Toward optimization of blood brain barrier opening induced by laser-activated perfluorocarbon nanodroplets

Effect of perfluorocarbon composition on activation of phase‐changing ultrasound contrast agents

Use of Physical Approaches for Systemic Drug Delivery

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