Internalization of targeted microbubbles by endothelial cells and drug delivery by pores and tunnels

Beekers, Inés; Langeveld, Simone A. G.; Meijlink, Bram; Steen, Antonius F.W. van der; Jong, Nico de; Verweij, Martin D.; Kooiman, Klazina

doi:10.1016/j.jconrel.2022.05.008

Cited by 17 publications

(12 citation statements)

References 66 publications

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“…This may be a consequence of cavitation offering a route to penetration of the DNA through both plasma and nuclear membranes. Such cavitation-mediated disruption of membranes, as reported and characterized by Liu et al over 2 decades ago, [36] has recently been elegantly captured by Beekers et al [37] The fact that the resulting anti-luciferase antibody response generated by cavitation-mediated delivery could match or surpass that achieved with needle and syringe is encouraging. Especially in the context of the relatively low amount of DNA actually reaching the dermal compartment, and the "dose-sparing" which may ultimately be possible if cavitation-mediated delivery can be further optimized.…”

Section: Discussionmentioning

confidence: 89%

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Cavitation‐Mediated Transcutaneous Delivery of Protein and Nucleotide‐based Antigen for Rapid High‐level Immune Responses

Hettinga,

Lyons,

Balkaran

et al. 2023

Advanced Therapeutics

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Alternatives are needed to remove the pain, injury, cross‐infection and hazardous waste associated with needle and syringe (N+S)‐based vaccination. Reported here is the use of novel ultrasound‐responsive protein cavitation nuclei (pCaN), formed using the model antigen bovine serum albumin (BSA), to achieve effective transcutaneous delivery. Upon exposure to ultrasound, these pCaN instigate cavitation events which propel themselves and co‐located DNA vectors into the skin. Ultrasound parameters as well as pCaN and DNA concentration were refined to achieve optimal expression of encoded luciferase transgene. Twenty‐four hours post‐treatment, luciferase expression in the skin, by IVIS imaging, was 1.67 × 106 ±941943, photons/sec for N+S intradermal injection and 1.49 × 106 ±261832 for cavitation‐mediated delivery (p>0.05). Hence, there was no significant difference in luciferase level achieved, but improved homogeneity and reproducibility of expression was evident in mice treated using ultrasound‐mediated cavitation. Despite this equivalence in luciferase levels, a >5x higher level (p<0.02) of anti‐luciferase antibodies was achieved when cavitation was used versus N+S injection. Antibody levels against BSA, resulting from use of BSA pCaN, were equivalent for the two groups. PCaN can be formed from a range of antigenic protein and DNA can encode a range of antigenic proteins, so this approach has wide‐ranging implications for needle‐free vaccination.This article is protected by copyright. All rights reserved

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Section: Discussionmentioning

confidence: 89%

“…Such cavitation‐mediated disruption of membranes, as reported and characterized by Liu et al over 2 decades ago, [ 36 ] has recently been elegantly captured by Beekers et al. [ 37 ]…”

Section: Discussionmentioning

confidence: 98%

Cavitation‐Mediated Transcutaneous Delivery of Protein and Nucleotide‐based Antigen for Rapid High‐level Immune Responses

Hettinga,

Lyons,

Balkaran

et al. 2023

Advanced Therapeutics

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“…Therefore, the targeted microbubble created pores and tunnels in the endothelial monolayer more efficiently than the non-targeted microbubbles ( Fig. 5 F) [113] .…”

Section: Vascular Effects Of Cavitation-mediated Barrier-breakingmentioning

confidence: 92%

“…(E) MB cavitation disrupted vascular endothelial cells and their tight contact [68] . (F) Internalization of targeted MBs into endothelial cells [113] . (G) Leakage of dextran molecules from different types of blood vessels (Top, arterioles; middle, venules; bottom, capillaries) after cavitation [114] .…”

Section: Vascular Effects Of Cavitation-mediated Barrier-breakingmentioning

confidence: 99%

Barrier-breaking effects of ultrasonic cavitation for drug delivery and biomarker release

Wei

Shen

Chen

et al. 2023

Ultrasonics Sonochemistry

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“…4A). 103 Related studies discovered that FUS combined with MB could enhance the brain delivery of edaravone and further improve the neuromuscular functions along with rescued muscle atrophy (Fig. 4B).…”

Section: Microbubble-assisted Drug Deliverymentioning

confidence: 98%

Ultrasound meets the cell membrane: for enhanced endocytosis and drug delivery

et al. 2023

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Internalization of targeted microbubbles by endothelial cells and drug delivery by pores and tunnels

Cited by 17 publications

References 66 publications

Cavitation‐Mediated Transcutaneous Delivery of Protein and Nucleotide‐based Antigen for Rapid High‐level Immune Responses

Cavitation‐Mediated Transcutaneous Delivery of Protein and Nucleotide‐based Antigen for Rapid High‐level Immune Responses

Barrier-breaking effects of ultrasonic cavitation for drug delivery and biomarker release

Ultrasound meets the cell membrane: for enhanced endocytosis and drug delivery

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