Ultrasound triggered phase-change nanodroplets for doxorubicin prodrug delivery and ultrasound diagnosis: An in vitro study.

Abstract

Ultrasound-triggered delivery system is among the various multifunctional and stimuli-responsive strategies that hold great potential as a robust solution to the challenges of localized drug delivery and gene therapy. In this work, we developed an ultrasound-triggered delivery system PFP/C9F17-PAsp(DET)/CAD/PGA-g-mPEG nanodroplet, which combined ultrasound responsive phase-change contrast agent, acid-cleavable doxorubicin prodrug and cationic amphiphilic fluorinated polymer carrier, aiming to achieve both high imaging contrast and preferable ultrasound-triggered anti-cancer therapeutic effect. The optimized nanodroplets were characterized as monodispersed particles with a diameter of about 400 nm, slightly positive surface charge and high drug-loading efficiency. The functional augmenter PGA-g-mPEG provided the nanodroplets good sustainability, low cytotoxicity and good serum compatibility, as confirmed by stability and biocompatibility tests. In ultrasound imaging study, the nanodroplets produced significant contrast with ultrasound irradiation (3.5 MHz, MI = 0.08) at 37 ℃. Cell uptake and cytotoxicity studies in HepG2 and CT-26 cells showed the enhanced drug uptake and therapeutic effect with the combination of nanodroplets and ultrasound irradiation. These results suggest that the PFP/CAD-loaded phase change nano-emulsion can be utilized as an efficient theranostic agent for both ultrasound contrast imaging and drug delivery.

• Authors: Jinbiao Gao, Baiqing Yu, Chao Li, Ming Xu, Zhong Cao, Xiaoyan Xie, Wei Wang, Jie Liu
• Journal: Colloids and surfaces. B, Biointerfaces (Colloids Surf B Biointerfaces) Vol. 174 Pg. 416-425 (Feb 01 2019) ISSN: 1873-4367 [Electronic] Netherlands
• PMID: 30481702 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Antibiotics, Antineoplastic
• Polymers
• Prodrugs
• Doxorubicin

Topics

• Antibiotics, Antineoplastic (chemistry, pharmacology)
• Colonic Neoplasms (diagnosis, diagnostic imaging, drug therapy)
• Doxorubicin (chemistry, pharmacology)
• Drug Delivery Systems
• Hep G2 Cells
• Humans
• Nanoparticles (administration & dosage, chemistry)
• Polymers (chemistry)
• Prodrugs (chemistry, pharmacology)
• Theranostic Nanomedicine
• Tumor Cells, Cultured
• Ultrasonography