Table 8 The different types of lipid nanoparticles used in mRNA vaccine delivery
From: The use of RNA-based treatments in the field of cancer immunotherapy
Lipid Nanoparticle Type | Advantages | Disadvantages | Immunogenicity | Efficacy | Safety | Stability | Mechanism of Action | Reference |
|---|---|---|---|---|---|---|---|---|
PEGylated lipids | Increased circulation time, reduced toxicity | Poor transfection efficiency, difficult to manufacture | Low | Moderate | High | Stable, but can be affected by PEG cleavage | Membrane fusion and endosomal escape | [520] |
Cationic lipids | Good transfection efficiency, easy to manufacture | Can be toxic, poor stability | High | High | Moderate | Can be unstable in solution | Electrostatic interactions with the cell membrane and endosomal escape | [466] |
Neutral lipids | High stability, low toxicity | Poor transfection efficiency | Low | Low | High | Stable | Endosomal escape | [480] |
pH-sensitive lipids | Endosomal escape in acidic environments, increased stability | Limited transfection efficiency, potential for off-target effects | High | Moderate | Moderate | Stable, but can be affected by pH changes | Endosomal escape in acidic environments | [521] |
Ionizable lipids | High transfection efficiency, good stability | Can be toxic, potential for off-target effects | High | High | Moderate | Stable | Endosomal escape via proton sponge effect | [2] |
Neutral pH-responsive lipids | Good transfection efficiency, endosomal escape in mild acidic conditions | Limited stability, potential for off-target effects | High | Moderate | Moderate | Stable, but can be affected by pH changes | Endosomal escape in mildly acidic environments | [135] |
Charge-reversal lipids | High transfection efficiency, good stability, increased target specificity | Potential for off-target effects, poor scalability | High | High | Moderate | Stable | Electrostatic interactions with the cell membrane and endosomal escape | [298] |
Multi-component lipids | Increased stability, reduced toxicity, improved transfection efficiency | Complex manufacturing process, can be expensive | High | High | High | Stable | Membrane fusion and endosomal escape | [522] |
PEG-phospholipid conjugates | Improved pharmacokinetics, increased stability | Poor transfection efficiency, limited control over PEG density | Low | Low | High | Stable | Membrane fusion and endosomal escape | [523] |
Ionizable cationic lipids | High transfection efficiency, low toxicity | Can be unstable, potential for off-target effects | High | High | Moderate | Stable | Endosomal escape via proton sponge effect and electrostatic interactions with the cell membrane | [262] |
Pro-nano liposomes | High stability, good transfection efficiency, biodegradable | Complex manufacturing process, potential for off-target effects | Moderate | High | Moderate | Stable | Endosomal escape and membrane fusion | [485] |
Dual-function polymer-lipid nanoparticles | High stability, improved transfection efficiency, reduced toxicity | Complex manufacturing process, limited understanding of mechanism | High | High | High | Stable | Endosomal escape and electrostatic interactions with the cell membrane | [524] |
SiRNA-lipid nanoparticles | Good transfection efficiency, high stability, reduced toxicity | Limited application to siRNA delivery only | Low | High | High | Stable | Endosomal escape and electrostatic interactions with the cell membrane | [341] |
Metal ion-mediated self-assembled lipid nanoparticles | High stability, good transfection efficiency | Limited understanding of mechanism, potential for toxicity | Low | Moderate | Moderate | Stable | Endosomal escape and membrane fusion | [525] |
Charge-altering releasable transporters (CARTs) | High transfection efficiency, improved target specificity, reduced toxicity | Limited understanding of mechanism, potential for off-target effects | High | High | High | Stable | Endosomal escape and membrane fusion | [298] |
Self-assembling RNA nanoliposomes | High stability, good transfection efficiency, low toxicity | Limited understanding of mechanism, potential for off-target effects | Low | High | High | Stable | Endosomal escape and membrane fusion | [442] |
Peptide amphiphile nanomicelles | High stability, reduced toxicity, improved transfection efficiency | Limited understanding of mechanism, potential for off-target effects | Low | High | High | Stable | Endosomal escape and membrane fusion | [526] |
pH-sensitive cationic liposomes | High transfection efficiency, improved stability, endosomal escape in mildly acidic environments | Limited understanding of mechanism, potential for off-target effects | High | High | Moderate | Stable | Endosomal escape in mildly acidic environments | [527] |
Phospholipid-PEG nanoparticles | Improved pharmacokinetics, reduced toxicity, good stability | Limited control over size and charge, limited transfection efficiency | Low | Low | High | Stable | Membrane fusion and endosomal escape | [523] |
Superparamagnetic iron oxide nanoparticles | Good stability, transfection efficiency, potential for simultaneous imaging and targeting | Potential for off-target effects, limited understanding of mechanism | Low | Moderate | Moderate | Stable | Endosomal escape and membrane fusion | [528] |
pH-sensitive liposomes | High transfection efficiency, improved stability, endosomal escape in mildly acidic environments | Limited understanding of mechanism, potential for off-target effects | High | High | Moderate | Stable | Endosomal escape in mildly acidic environments | [307] |
Lipid-like nanoparticles | Good stability, transfection efficiency, reduced toxicity | Limited understanding of mechanism, potential for off-target effects | Low | High | High | Stable | Endosomal escape and membrane fusion | [341] |
Cationic lipid-polymer hybrid nanoparticles | High stability, improved transfection efficiency, reduced toxicity | Complex manufacturing process, potential for off-target effects | High | High | Moderate | Stable | Endosomal escape and electrostatic interactions with the cell membrane | [190] |
PEGylated lipid nanoparticles | Improved pharmacokinetics, reduced toxicity, good stability | Limited control over size and charge, limited transfection efficiency | Low | Low | High | Stable | Membrane fusion and endosomal escape | [473] |
Targeted lipid nanoparticles | Improved target specificity, high stability, good transfection efficiency | Complex manufacturing process, potential for off-target effects | High | High | Moderate | Stable | Endosomal escape and specific receptor-mediated endocytosis | [529] |
Unilamellar liposomes | High transfection efficiency, good stability, reduced toxicity | Limited control over size and charge, potential for off-target effects | Moderate | High | High | Stable | Endosomal escape and membrane fusion | [459] |
Cationic lipid-nucleic acid nanoparticles | High transfection efficiency, improved stability, reduced toxicity | Complex manufacturing process, potential for off-target effects | High | High | Moderate | Stable | Endosomal escape and electrostatic interactions with the cell membrane | [530] |
Silica nanoparticles | Good stability, transfection efficiency, potential for simultaneous imaging and targeting | Limited understanding of mechanism, potential for toxicity | Low | Moderate | Moderate | Stable | Endosomal escape and membrane fusion | [531] |
Lipopolyplex nanoparticles | High transfection efficiency, improved stability, reduced toxicity | Complex manufacturing process, potential for off-target effects | High | High | Moderate | Stable | Endosomal escape and electrostatic interactions with the cell membrane | [532] |
Calcium phosphate nanoparticles | Good stability, potential for simultaneous imaging and targeting | Limited transfection efficiency, potential for toxicity | Low | Moderate | Moderate | Stable | Endosomal escape and membrane fusion | [444] |