Table 1.
Summary of methods for delivery of trehalose into mammalian cells and their corresponding advantages and disadvantages.
| Method | Advantages | Disadvantages |
|---|---|---|
| Phospholipid-Phase Transition via thermal, osmotic, or electric stress6–17 | Control of trehalose loading by manipulating concentration gradient Increasing membrane permeability |
Non-specific membrane permeability Cytotoxicity and membrane stability concerns due to thermal, osmotic, and electric shock to cells |
| Fluid-Phase Endocytosis22–24 | Taking advantage of the natural cell uptake process | Long incubation time Loading only small amounts of trehalose |
| Gene expression25,26 | Endogenous expression of trehalose | Adenoviral vector cytotoxicity Requiring genetic modification of cells |
| Engineered pores and channels27–32 | Reversible based on external stimuli Controllable influx of trehalose by manipulating concentration gradient |
Non-specific membrane permeability Use of exogenous, bacterial derived-protein Overstimulation of ATP receptors linked to apoptosis, necrosis, neoplasia |
| TRET1 Transporter33,34 | Selective transport of trehalose across membrane | Requiring genetic modification of cells |
| Microinjection35–38 | Direct insertion of controlled amount of trehalose into large cells such as oocytes and early embryos | Not practical for small somatic cells or large number of cells |
| Polymers and peptides39–44 | Loading high amounts of intracellular trehalose Increasing membrane permeability |
Non-specific membrane permeability Long incubation time Cytotoxicity concerns |
| Liposomes45–47 | Biocompatible with cell membrane | Loading only small amounts of trehalose Poor stability |
| Nanoparticles48,49 | Specific transport of high amounts of trehalose Utilizing endocytosis that is the natural process of cell eating No modification to cells |
Long (up to 1 day) incubation time |
| Ultrasound50 | Increased membrane permeability |
Affects cell morphology Non-specific membrane permeability |
| Engineered trehalose51 | Trehalose-derivative becomes permeable to cells Natural machinery can digest derivative into trehalose |
Possible build-up of trehalose-derivative due to limiting esterases |