Recent Developments of Liposomes as Nanocarriers for Theranostic Applications

Abstract

Liposomes are nanocarriers comprised of lipid bilayers encapsulating an aqueous core. The ability of liposomes to encapsulate a wide variety of diagnostic and therapeutic agents has led to significant interest in utilizing liposomes as nanocarriers for theranostic applications. In this review, we highlight recent progress in developing liposomes as nanocarriers for a) diagnostic applications to detect proteins, DNA, and small molecule targets using fluorescence, magnetic resonance, ultrasound, and nuclear imaging; b) therapeutic applications based on small molecule-based therapy, gene therapy and immunotherapy; and c) theranostic applications for simultaneous detection and treatment of heavy metal toxicity and cancers. In addition, we summarize recent studies towards understanding of interactions between liposomes and biological components. Finally, perspectives on future directions in advancing the field for clinical translations are also discussed.

Keywords: clinical translation.; liposomes; multimodal imaging; targeted therapy; theranostics.

Figure 1

An overview of the discovery, development, and evolution of liposomes since their first report in 1965.

Figure 2

(a) Left: Schematic of a PEGylated liposome with NIR-fluorescent Y₂O₃:Er³⁺ nanoparticles encapsulated. Right: NIR fluorescence microscopic images of histological sections of various organs of a mouse injected with different liposomal Y₂O₃:Er³⁺ nanoparticles. Figures adapted with permission from Ref. . (b) Left: Schematic of a Ferri-liposome. Right: T2-weighted MR images of a transgenic mouse before and 1 h and 48 h after intraperitoneal injection of Ferri-liposomes followed by 1 h of magnetic field application to the lower right tumor (white arrow). Reprinted by permission from Macmillan Publishers Ltd: Nature Nanotechnology , copyright 2011.

Figure 3

(a) Scheme of stimuli-responsive liposomes responsive to small molecule targets, incorporating multimodal detection. Calibration curve for detection of cocaine via (b) fluorescence detection and (c) MRI detection using stimuli-responsive liposomes. Reprinted with permission from Ref. . Copyright 2016 American Chemical Society.

Figure 4

(a) Left: Schematic of AS1411 aptamer-modified liposomal DOX. Right: Confocal fluorescence images of MCF-7 cells in tumor sections showing in vivo tumor penetration ability of aptamer-liposomes. Reproduced from Ref. with permission from the Royal Society of Chemistry. (b) Left: Schematic of a nanochain structure consists of one liposome and three iron oxide nanoparticles. Right: Fluorescence images of a histological section of mouse 4T1 tumor 48 h after intravenous injection of liposomal DOX, with and without RF treatment. Reprinted with permission from Ref. . Copyright 2012 American Chemical Society. (c) Left: Schematic of a multifunctional liposome with c(RGDyK) modification on surface and paclitaxel encapsulated. Right: T1-weighted MR images of a mouse before and after treatment with the multifunctional liposome. Reproduced from Ref. with permission from the Royal Society of Chemistry.

Figure 5

(a) A multiplexed and high-throughput protein-lipid interaction assay to measure protein recruitment to liposome membranes. Reprinted by permission from Macmillan Publishers Ltd: Nature Method , copyright 2014. (b) Scheme showing the surface based fluorescence assay to study the assembly of liposome-polydopamine coatings and the interaction with myoblast cells. Reprinted with permission from Ref. . Copyright 2011 American Chemical Society.

Figure 6

(a) Scheme of the nanoparticles formulated from lipidoid, cholesterol, DSPC (phospholipid), PEG2000-DMG and siRNA; (b) Combinatorial addition chemistry of alkyl-amines to alkyl-acrylate; (c) Ninety-six nanoparticles were tested for siRNA delivery to hepatocytes in mice. Eighty-eight percent of nanoparticles fitting three structural parameters achieved nearly complete gene knockdown; (d) pKa values significantly influenced siRNA delivery efficacy of nanoparticles. Reprinted by permission from Macmillan Publishers Ltd: Nature Communications , copyright 2014.