Lipid nanobubbles as an ultrasound-triggered artesunate delivery system for imaging-guided, tumor-targeted chemotherapy
Authors Gao S, Cheng X, Li J
Received 10 October 2018
Accepted for publication 4 December 2018
Published 6 March 2019 Volume 2019:12 Pages 1841—1850
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Amy Norman
Peer reviewer comments 3
Editor who approved publication: Dr Takuya Aoki
Shuang Gao,1,* Xiaohui Cheng,2,* Jinhua Li3
1Ultrasound Department, Guilin People’s Hospital, Guilin, Guangxi 541002, China; 2Department of Clinical Pharmacy, Daqing Oilfield General Hospital, Daqing, Heilongjiang 163000, China; 3Traditional Chinese Medicine Department, Gansu Provincial Hospital, Lanzhou, Gansu 730000, China
*These authors contributed equally to this work
Purpose: Herein, this study is to prepare folic acid (FA)-conjugated lipid nanobubbles (NBs) that highly load artesunate (Arte; FA-ALNBs), as an ultrasound (US)-triggered Arte delivery system for imaging-guided, tumor-targeted chemotherapy.
Materials and methods: The morphology, size, zeta potential, and stability of the FA-ALNBs were detected by optical microscopy and dynamic light scattering analysis. The cellular uptake of the FA-ALNBs was evaluated by confocal laser scanning microscopy and flow cytometry.
Results: The FA-ALNBs showed uniform spheroidal structure, with 781.2±5.3 nm in average diameter, great physiological stability, and ~91.9%±1.1% encapsulation efficiency of Arte. Using focused US, about 36.1%±2.5% of the entrapped Arte was trigger-released from the FA-ALNBs. Owing to the US contrast property, FA-ALNBs showed an enhanced US signal in vitro when using an ultrasonic diagnostic apparatus with a 1-MHz linear transducer. Due to the FA receptor-mediated endocytosis effect, FA-ALNBs can be efficiently internalized by cells, showing an uptake ratio of about 56.4%±3.1%. FA-ALNBs showed an enhanced, dose-dependent cell-killing ability, while FA-ALNBs plus US irradiation exhibited a stronger anticancer effect in vitro. Post intravenous injection into tumor-bearing mice, FA-ALNBs showed an enhanced US contrast effect with increase in time, indicating the increasing accumulation of FA-ALNBs in tumor tissue, which peaked at 4 hours post injection. Focused US irradiation was conducted on the tumor region at 4 hours post injection of FA-ALNBs, which showed a greater tumor suppression effect after 30 days of treatment compared with all other treatment groups. Moreover, FA-ALNBs showed negligible systemic toxicity in vivo.
Conclusion: This versatile US-triggered drug delivery system with great anticancer efficacy was assessed both in vitro and in vivo, revealing great potential as a cancer theranostic agent for future application.
Keywords: nanobubbles, artesunate, ultrasound imaging, ultrasound-triggered drug release, cancer theranostics
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]