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. 2023 Jul 7;22:106. doi: 10.1186/s12943-023-01807-w

Table 8.

The different types of lipid nanoparticles used in mRNA vaccine delivery

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]