Sudden Cell Death Induced by Ca2+ Delivery via Microbubble Cavitation

Maciulevičius, Martynas; Navickaitė, Diana; Chopra, Sonam; Jakštys, Baltramiejus; Šatkauskas, Saulius

doi:10.3390/biomedicines9010032

Cited by 7 publications

(5 citation statements)

References 35 publications

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“…In addition, it has been demonstrated that increasing activation firings and duty cycles induce cell death during the sonoporation process 39–41 . Continuous inertial cavitations have also been reported to induce the production of reactive oxygen species or suddenly evoke calcium influx to cause cell death 29,32 . Accordingly, the optical and acoustic parameters need to be carefully selected to achieve effective sonoporation while minimizing cell death.…”

Section: Discussionmentioning

confidence: 99%

“…[39][40][41] Continuous inertial cavitations have also been reported to induce the production of reactive oxygen species or suddenly evoke calcium influx to cause cell death. 29,32 Accordingly, the optical and acoustic parameters need to be carefully selected to achieve effective sonoporation while minimizing cell death.…”

Section: Discussionmentioning

confidence: 99%

“…However, cavitation has still been generally determined as an effect hard to be controlled and predicted in some cases, 26 and cell damage typically induced by bioeffects or the mechanical actions of the cavitation bubbles. [27][28][29][30][31][32][33] We thus aim to explore the possibility of inducing sonoporation based on repeated vaporization to reduce the required driving energy for an improved therapeutic strategy in an efficient and safe manner, and also may improve the performance of image-guided theragnosis.…”

Section: Introductionmentioning

confidence: 99%

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Sonoporation based on repeated vaporization of gold nanodroplets

Liu

2022

Medical Physics

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Background: Gold nanodroplets (AuNDs) have been proposed as agents for photothermal therapy and photoacoustic imaging. Previously, we demonstrated that the sonoporation can be more effectively achieved with synchronized optical and acoustic droplet vaporization. By applying a laser pulse at the rarefactional phase of the ultrasound (US) pulse, the vaporization threshold can be reached at a considerably lower laser average power. However, a large loading quantity of the AuNDs may increase the risk of air embolism. The destruction of phase-shifted AuNDs at the inertial cavitation stage leads to a reduced drug delivery performance. And it also causes instability of echogenicity during therapeutic monitoring. Purpose: In this study,we propose to further improve the sonoporation effectiveness with repeated vaporization. In other words, the AuNDs repeatedly undergo vaporization and recondensation so that sonoporation effects are accumulated over time at lower energy requirements. Previously, repeated vaporization has been demonstrated as an imaging contrast agent. In this study, we aim to adopt this repeated vaporization scheme for sonoporation. Methods: Perfluoropentane NDs with a shell made of human serum albumin were used as the US contrast agents. Laser pulses at 808 nm and US pulses of 1 MHz were delivered for triggering vaporization and inertial cavitation of NDs. We detected the vaporization and cavitation effects under different activation firings, US peak negative pressures (PNPs), and laser fluences using 5-and 10-MHz focused US receivers. Numbers of calcein-AM and propidium iodide signals uptake by BNL hepatocarcinoma cancer cells were used to evaluate the sonoporation and cell death rate of the cells. Results: We demonstrate that sonoporation can be realized based on repeatable vaporization instead of the commonly adopted inertial cavitation effects. In addition, it is found that the laser fluence and the acoustic pressure can be reduced. As an example, we demonstrate that the acoustic and optical energy for achieving a similar level of sonoporation rate can be as low as 0.44 MPa for the US PNP and 4.01 mJ/cm 2 for the laser fluence, which are lower than those with our previous approach (0.53 MPa and 4.95 mJ/cm 2 , respectively). Conclusion:We demonstrated the feasibility of vaporization-based sonoporation at a lower optical and acoustic energy. It is an advantageous method that can enhance drug delivery efficiency, therapeutic safety and potentially deliver an upgraded gene therapy strategy for improved theragnosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sonoporation based on repeated vaporization of gold nanodroplets

Liu

2022

Medical Physics

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“…Calcium ion delivery, enhanced by different intracellular delivery modalities, such as electroporation (EP) [ 14 , 15 ] and SP [ 16 ], has been proposed as a favorable alternative to regular chemotherapy. A plethora of extracellular stimuli are able to implicitly increase the intracellular level of diffusible Ca 2+ , which, in turn, acts as a second messenger and controls a milieu of intrinsic cellular processes, including the mechanism of cell death.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, in comparison to traditional chemotherapy, the employment of US-MB-mediated delivery of supra-physiological Ca 2+ levels for cancer treatment can significantly diminish the serious after-effects inflicted by conventional cytotoxic drugs, particularly following intravascular or oral administration. However, Ca 2+ delivery and possible therapeutic applications are poorly investigated in the field of SP, except for our previous work [ 16 ]. Therefore, in the first part of our research, we aimed to determine the possible Ca 2+ applications for chemotherapy by comparing the levels of cell death induced in Chinese hamster ovary (CHO) cells by both Ca 2+ and BLM after SP.…”

Section: Introductionmentioning

confidence: 99%

The Assessment of Calcium and Bleomycin Cytotoxic Efficiency in Relation to Cavitation Dosimetry

et al. 2023

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Microbubble (MB)- and ultrasound (US)-facilitated intracellular Ca2+ delivery, known as sonoporation (SP), is a promising anticancer treatment modality, since it allows a spatio-temporally controllable and side-effect-free alternative to conventional chemotherapy. The current study provides extensive evidence that a 5 mM concentration of Ca2+ in combination with US alone or US and Sonovue MBs can be an alternative to the conventional 20 nM concentration of the anticancer drug bleomycin (BLM). Ca2+ application together with SP induces a similar level of death in Chinese hamster ovary cells to the combination of BLM and SP but does not cause systemic toxicity, as is inherent to conventional anticancer drugs. In addition, Ca2+ delivery via SP alters three vital characteristics essential for viable cells: membrane permeability, metabolic activity and proliferation ability. Most importantly, Ca2+ delivery via SP elicits sudden cell death—occurring within 15 min—which remains similar during 24–72 h and 6 d periods. The extensive study of US waves side-scattered by MBs led to the quantification of the cavitation dose (CD) separately for subharmonics, ultraharmonics, harmonics and broadband noise (up to 4 MHz). The CD was suitable for the prognostication of the cytotoxic efficiency of both anticancer agents, Ca2+ and BLM, as was indicated by an overall high (R2 ≥ 0.8) correlation (22 pairs in total). These extensive analytical data imply that a broad range of frequencies are applicable for the feedback-loop control of the process of US-mediated Ca2+ or BLM delivery, successively leading to the eventual standardization of the protocols for the sonotransfer of anticancer agents as well as the establishment of a universal cavitation dosimetry model.

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