Jumping acoustic bubbles on lipid bilayers

Loughian, Christelle Der; Seya, Pauline Muleki; Pirat, Christophe; Inserra, Claude; Béra, Jean‐Christophe; Rieu, Jean-Paul

doi:10.1039/c5sm00427f

Cited by 2 publications

(2 citation statements)

References 33 publications

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“…5,6 Recent studies have reported the shedding of surface material from phospholipid-coated MBs, 7 the deposition of liposomal lipids onto cell membranes, 8 and the transfer of lipids from phospholipid-shelled MBs to synthetic membranes during ultrasound excitation in vitro. 9 Previous work by the authors has also shown that lipid transfer from MBs to cell membranes influences membrane hydration and lipid order. 10 Critically, this effect was found to be highly dependent on the MB formulation (i.e., carrier lipid chain length, emulsifier species, and molar ratio of lipid to emulsifier).…”

Section: Introductionmentioning

confidence: 92%

“…Exposure to microbubbles (MBs) and ultrasound can induce an increase in cell permeability (sonoporation) offering a promising modality for noninvasively increasing the local uptake of therapeutics in a range of applications, including cancer and neurodegenerative diseases. − A range of potential mechanisms have been proposed to explain the process of sonoporation, but this remains an area of active research. , Recent studies have reported the shedding of surface material from phospholipid-coated MBs, the deposition of liposomal lipids onto cell membranes, and the transfer of lipids from phospholipid-shelled MBs to synthetic membranes during ultrasound excitation in vitro . Previous work by the authors has also shown that lipid transfer from MBs to cell membranes influences membrane hydration and lipid order .…”

Section: Introductionmentioning

confidence: 99%

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Investigating the Role of Lipid Transfer in Microbubble-Mediated Drug Delivery

et al. 2019

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Sonoporation, the permeabilization of cell membranes following exposure to microbubbles and ultrasound, has considerable potential for therapeutic delivery. To date, engineering of microbubbles for these applications has focused primarily upon optimizing microbubble size and stability, or attachment of targeting species and/or drug molecules. In this work, it is demonstrated that the microbubble coating can also be tailored to directly influence cell permeabilization. Specifically, lipid exchange mechanisms between phospholipid microbubbles and cells can be exploited to significantly increase sonoporation efficiency in vitro. A theoretical analysis of the energy required for pore formation was carried out. From this, it was hypothesized that sonoporation could be promoted by the transfer of lipid molecules with appropriate carbon chain length and/or shape (cylindrical or conical). Spectral imaging with a hydration-sensitive membrane probe (C-Laurdan) was used to measure changes in the membrane lipid order of A-549 cancer cells following exposure to suspensions of different phospholipids. Two candidate lipids were identified, a short-chain-length phospholipid (1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC)) and a medium-chain-length lysolipid (1-palmitoyl-2hydroxy-sn-glycero-3-phosphocholine (16:0 lyso-PC)). Microbubbles were prepared with matched concentrations, size distributions, and acoustic responses. Confocal microscopy was used to measure cell uptake of a model drug (propidium iodide) with and without ultrasound exposure (1 MHz, 250 kPa peak negative pressure, 1 kHz pulse repetition frequency, 10% duty cycle, 15 s exposure). Despite significantly decreasing the cell membrane lipid order, DLPC did not increase sonoporation. Microbubbles containing 16:0 lyso-PC, however, produced a ∼5-fold increase in sonoporation compared to control microbubbles. Importantly, the lyso-PC molecules were incorporated into the microbubble coating and did not affect cell permeability prior to ultrasound exposure. These findings indicate that microbubbles can be engineered to exploit lipid exchange between microbubble shells and cell membranes to enhance drug delivery, a new optimization route that may lead to enhanced therapeutic efficacy of ultrasound-mediated treatments.

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Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Investigating the Role of Lipid Transfer in Microbubble-Mediated Drug Delivery

et al. 2019

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Modulation of the molecular arrangement in artificial and biological membranes by phospholipid-shelled microbubbles

et al. 2017

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The transfer of material from phospholipid-coated microbubbles to cell membranes has been hypothesized to play a role in ultrasound-mediated drug delivery. In this study, we employed quantitative fluorescence microscopy techniques to investigate this phenomenon in both artificial and biological membrane bilayers in an acoustofluidic system. The results of the present study provide strong evidence for the transfer of material from microbubble coatings into cell membranes. Our results indicate that transfer of phospholipids alters the organization of molecules in cell membranes, specifically the lipid ordering or packing, which is known to be a key determinant of membrane mechanical properties, protein dynamics, and permeability. We further show that polyethylene-glycol, used in many clinical microbubble formulations, also has a major impact on both membrane lipid ordering and the extent of lipid transfer, and that this occurs even in the absence of ultrasound exposure.

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Jumping acoustic bubbles on lipid bilayers

Cited by 2 publications

References 33 publications

Investigating the Role of Lipid Transfer in Microbubble-Mediated Drug Delivery

Investigating the Role of Lipid Transfer in Microbubble-Mediated Drug Delivery

Modulation of the molecular arrangement in artificial and biological membranes by phospholipid-shelled microbubbles

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