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Citation
Tags
HERO ID
7175237
Reference Type
Journal Article
Title
Microfluidic synthesis of multifunctional liposomes for tumour targeting
Author(s)
Ran, Rui; Middelberg, APJ; Zhao, CXia; ,
Year
2016
Is Peer Reviewed?
Yes
Journal
Colloids and Surfaces B: Biointerfaces
ISSN:
0927-7765
EISSN:
1873-4367
Publisher
ELSEVIER SCIENCE BV
Location
AMSTERDAM
Page Numbers
402-410
PMID
27639490
DOI
10.1016/j.colsurfb.2016.09.016
Web of Science Id
WOS:000388248500046
Abstract
Nanotechnology has started a new era in engineering multifunctional nanoparticles for diagnosis and therapeutics by incorporating therapeutic drugs, targeting ligands, stimuli-responsive release and imaging molecules. However, more functionality requires more complex synthesis processes, resulting in poor reproducibility, low yield and high production cost, hence difficulties in clinical translation. Herein we report a one-step microfluidic method for making multifunctional liposomes. Three formulations were prepared using this simple method, including plain liposomes, PEGylated liposomes and folic acid functionalised liposomes, all with a fluorescence dye encapsulated for imaging. The size and surface properties of these liposomes can be precisely controlled by simply tuning the flow rate ratio and the ratio of the lipids to PEGylated lipid (DSPE-PEG(2000)) and to the DSPE-PEG(2000)-Folate, respectively. The synthesised liposomes remained stable under mimic serum conditions. Compared to the plain liposomes and PEGylated liposomes, the targeted folic acid functionalised liposomes exhibited enhanced cellular uptake by the FA receptor positive SKOV3 cells, but not the negative MCF7 cells, and this enhanced uptake could be inhibited by adding excess free folic acid, indicating high specificity of FA ligand-receptor endocytosis. Further evaluation using the 3D tumour spheroid model also showed higher internalisation of the targeted liposome formulation in comparison with the PEGylated one. To the best of our knowledge, this work demonstrates for the first time the versatility of this microfluidic method for making different liposome formulations in a single step, their superior physicochemical properties as well as the enhanced cellular uptake and tumour spheroid uptake of the targeted liposomes. (C) 2016 Elsevier B.V. All rights reserved.
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