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. 2023 Jul 1:565:216220.
doi: 10.1016/j.canlet.2023.216220. Epub 2023 May 19.

Advances in lipid-based carriers for cancer therapeutics: Liposomes, exosomes and hybrid exosomes

Disha N Moholkar  1 , Raghuram Kandimalla  2 , Ramesh C Gupta  3 , Farrukh Aqil  4
Affiliations

Advances in lipid-based carriers for cancer therapeutics: Liposomes, exosomes and hybrid exosomes

Disha N Moholkar et al. Cancer Lett. .

Abstract

Cancer has recently surpassed heart disease as the leading cause of deaths worldwide for the age group 45-65 and has been the primary focus for biomedical researchers. Presently, the drugs involved in the first-line cancer therapy are raising concerns due to high toxicity and lack of selectivity to cancer cells. There has been a significant increase in research with innovative nano formulations to entrap the therapeutic payload to enhance efficacy and eliminate or minimize toxic effects. Lipid-based carriers stand out due to their unique structural properties and biocompatible nature. The two main leaders of lipid-based drug carriers: long known liposomes and comparatively new exosomes have been well-researched. The similarity between the two lipid-based carriers is the vesicular structure with the core's capability to carry the payload. While liposomes utilize chemically derived and altered phospholipid components, the exosomes are naturally occurring vesicles with inherent lipids, proteins, and nucleic acids. More recently, researchers have focused on developing hybrid exosomes by fusing liposomes and exosomes. Combining these two types of vesicles may offer some advantages such as high drug loading, targeted cellular uptake, biocompatibility, controlled release, stability in harsh conditions and low immunogenicity.

Keywords: Cancer therapeutics; Exosomes; Fusion; Hybrid exosomes; Lipid-based vesicles; Liposomes.

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Conflict of interest statement

Declaration of competing interest Dr. Ramesh C. Gupta holds positions both at the University of Louisville and 3P Biotechnologies, Inc. The authors have filed an international patent application (PCT) based on part of the results reported in this paper. All other authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.
Classification of lipid-based nanocarriers based on their structure and composition. Liposomes, exosomes, and hybrid exosomes exhibit core shell structure enclosed in a lipid bilayer, while microemulsions, nanoemulsions, nanocapsules, micelles and lipid nanoparticles comprise a mono layer of phospholipids to entrap the drug of interest in its lumen.
Figure 2.
Figure 2.
Diversity of exosomes sources and method of exosomes isolation as reported in literature.
Figure 3.
Figure 3.
Tissue distribution of exosomes (Exo) and folic acid (FA)-functionalized exosomes (FA-Exo). Folate receptor levels in NSCLC cells in vitro and lung and lung tumor tissues in nude mice, as analyzed by western blot (A). A549-tumor-bearing mice were treated with AF750-labeled Exo and FA-Exo intravenously. Different tissues and tumors were imaged ex vivo after 4 h of the treatment (B). Data for the fluorescence signals represent mean ± SD (n=3). The figure is partially adopted and redrawn from Munagala et al., 2021 [168].
Figure 4.
Figure 4.
Schematic diagram showing the fusion of exosomal and liposomal bilayer to form hybrid exosomes.
Figure 5.
Figure 5.
Flowchart of different methods of formation of hybrid exosomes by fusion of lipid thin film with exosomes. Fusion with lipids can occur either by direct addition of exosomes for the hydration of the lipid thin film [190] or via the addition of exosomes to the preformed liposomes followed by freeze-thaw cycles [191], simple mixing and incubation [25] or sonication followed by extrusion [192].
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