Sonoprinting liposomes on tumor spheroids by microbubbles and ultrasound

JOURNAL OF CONTROLLED RELEASE

卷:316

Article

Roovers, S.^1,2  Deprez, J.^1,2  Priwitaningrum, D.^3,4  Lajoinie, G.^4,5  Rivron, N.⁶  Declercq, H.^2,7  De Wever, O.^2,8  Stride, E.⁹  Le Gac, S.^4,10  Versluis, M.^4,5  Prakash, J.^3,4  De Smedt, S. C.^1,2  Lentacker, I.^1,2 

[1] Univ Ghent, Ghent Res Grp Nanomed, Lab Gen Biochem & Phys Pharm, Ghent, Belgium

[2] CRIG, Ghent, Belgium

[3] Univ Twente, MESA Inst Nanotechnol, Dept Biomat Sci & Technol, Targeted Therapeut, Enschede, Netherlands

[4] Univ Twente, Tech Med TechMed Ctr, Enschede, Netherlands

[5] Univ Twente, MESA Inst Nanotechnol, Phys Fluids Grp, Enschede, Netherlands

[6] Austrian Acad Sci, Inst Mol Biotechnol, Vienna, Austria

[7] Univ Ghent, Dept Human Struct & Repair, Tissue Engn Grp, Ghent, Belgium

[8] Univ Ghent, LECR, Ghent, Belgium

[9] Univ Oxford, Inst Biomed Engn, Dept Engn Sci, Oxford, England

[10] Univ Twente, MESA Inst Nanotechnol, Appl Microfluid BioEngn Res, Enschede, Netherlands

关键词: Microbubbles;    Ultrasound;    Drug delivery;    Loaded Microbubbles;    Mechanisms;    Sonoprinting;   

DOI  :  10.1016/j.jconrel.2019.10.051

来源: Elsevier

【 摘 要 】

Ultrasound-triggered drug-loaded microbubbles have great potential for drug delivery due to their ability to locally release drugs and simultaneously enhance their delivery into the target tissue. We have recently shown that upon applying ultrasound, nanoparticle-loaded microbubbles can deposit nanoparticles onto cells grown in 2D monolayers, through a process that we termed sonoprinting. However, the rigid surfaces on which cell monolayers are typically growing might be a source of acoustic reflections and aspherical microbubble oscillations, which can influence microbubble-cell interactions. In the present study, we aim to reveal whether sonoprinting can also occur in more complex and physiologically relevant tissues, by using free-floating 3D tumor spheroids as a tissue model. We show that both monospheroids (consisting of tumor cells alone) and cospheroids (consisting of tumor cells and fibroblasts, which produce an extracellular matrix) can be sonoprinted. Using doxorubicin-liposome-loaded microbubbles, we show that sonoprinting allows to deposit large amounts of doxorubicin-containing liposomes to the outer cell layers of the spheroids, followed by doxorubicin release into the deeper layers of the spheroids, resulting in a significant reduction in cell viability. Sonoprinting may become an attractive approach to deposit drug patches at the surface of tissues, thereby promoting the delivery of drugs into target tissues.

【 授权许可】

Free