Table 6 The comparison of various mRNA cancer vaccine delivery systems
From: The use of RNA-based treatments in the field of cancer immunotherapy
Delivery System | Advantages | Disadvantages | Immunogenicity | Efficacy | Safety | Stability | Reference |
|---|---|---|---|---|---|---|---|
Lipid nanoparticles (LNPs) | High delivery efficiency, increased cellular uptake, and low toxicity | Prone to degradation, manufacturing costs, potential for immune response | Potentially high immunogenicity, excellent antigen expression | Vary depending on the specific cancer target and delivery method | Generally safe with limited adverse effects reported | Susceptible to degradation and require specialized storage conditions | [2] |
Cationic polymers | Low cost, easy to produce, and highly customizable | Relatively low transfection efficiency and potential for toxicity | Lower immunogenicity than LNPs, but highly dependent on the specific polymer used | Highly dependent on cancer target and delivery method | Generally safe, but potential for toxicity and adverse immune responses | Vary depending on the specific polymer used | [121] |
Peptide-based delivery | Highly customizable, and potential for targeted delivery | Low transfection efficiency and potential for toxicity | Potentially high immunogenicity, but dependent on the specific peptide used | Highly dependent on the cancer target and peptide delivery method | Generally safe, but potential for toxicity and adverse immune responses | Susceptible to degradation and require specialized storage conditions | [74] |
In vivo electroporation (EP) | High transfection efficiency and targeted delivery | Limited depth of delivery, potential for pain or discomfort during injection, and potential for immune response | Potentially high immunogenicity, but highly dependent on the specific EP conditions and mRNA target | Highly dependent on cancer target and delivery method, but may have potential for both local and systemic effects | Generally safe, but potential for toxicity and adverse immune responses | Susceptible to degradation and require specialized storage conditions | [123] |
Physical delivery methods (e.g., laser microporation, sonoporation) | Highly targeted delivery and relatively non-invasive compared to injection | Limited depth of delivery and potential for immune response | Highly dependent on the specific method and cancer target | Vary depending on the specific method and cancer target | Generally safe, but potential for toxicity and adverse immune responses | Vary depending on the specific method and cancer target | [111] |
Gold nanoparticles | Targeted delivery and potential for imaging and therapeutic applications | May have potential for toxicity and immune response | May have lower immunogenicity compared to other delivery methods, but highly dependent on the specific conditions and mRNA target | Highly dependent on cancer target and delivery method, but may have potential for both local and systemic effects | Generally safe, but potential for toxicity and adverse immune responses | Vary depending on the specific method and cancer target | [133] |
Biodegradable microspheres | Prolonged release and targeted delivery | Limited depth of delivery and potential for immune response | Potentially high immunogenicity, but highly dependent on the specific microsphere and mRNA target | Highly dependent on cancer target and delivery method | Generally safe, but potential for toxicity and adverse immune responses | Vary depending on the specific microsphere and cancer target | [161] |
Cell-based vaccines | May have potential for enhanced efficacy and long-term immunity | May be challenging to produce and standardize, potential for immune response, and limited shelf-life | Highly dependent on the specific cell-based vaccine and mRNA target | Highly dependent on cancer target and delivery method | Generally safe, but potential for toxicity and adverse immune responses | Vary depending on the specific vaccine and cancer target | [123] |
Proteins and peptides | High specificity and potential for targeted delivery | Low transfection efficiency and potential for toxicity | Potentially high immunogenicity, but highly dependent on the specific protein or peptide used | Highly dependent on cancer target and delivery method | Generally safe, but potential for toxicity and adverse immune responses | Vary depending on the specific protein or peptide and cancer target | [123] |
Electrospray | High encapsulation efficiency, tunable particle size and morphology, and high antigenicity | Potential for mRNA degradation and low transfection efficiency | Potentially high immunogenicity, but dependent on the specific conditions and mRNA target | Highly dependent on cancer target and delivery method, but may have potential for both local and systemic effects | Generally safe, but potential for toxicity and adverse immune responses | Susceptible to degradation and require specialized storage conditions | [135] |
RNA-lipoplexes | High delivery efficiency and low toxicity | Potentially low immunogenicity and low transfection efficiency | Potentially low immunogenicity and low transfection efficiency | Highly dependent on cancer target and delivery method | Generally safe, but potential for toxicity and adverse immune responses | Susceptible to degradation and require specialized storage conditions | [121] |
mRNA-coated gold nanorods | Targeted delivery, potential for enhanced photothermal therapy, and reduced toxicity | Potentially low immunogenicity and low transfection efficiency | Potentially low immunogenicity and low transfection efficiency | Highly dependent on cancer target and delivery method | Generally safe, but potential for toxicity and adverse immune responses | Susceptible to degradation and require specialized storage conditions | [133] |
Nanocarriers (e.g., dendrimers, cyclodextrins) | High encapsulation efficiency and low toxicity | May have potential for immune response, potential for mRNA degradation, and limited efficacy | Potentially high immunogenicity, but dependent on the specific carrier and mRNA target | Highly dependent on cancer target and delivery method | Generally safe, but potential for toxicity and adverse immune responses | Susceptible to degradation and require specialized storage conditions | [463] |
Lipoplex-like nanoparticle | High encapsulation efficiency, low toxicity, and enhanced efficacy | May have potential for immune response and limited stability | Potentially high immunogenicity, but dependent on the specific nanoparticle and mRNA target | Highly dependent on cancer target and delivery method | Generally safe, but potential for toxicity and adverse immune responses | Susceptible to degradation and require specialized storage conditions | [121] |
Lipid-coated gold nanorods | Targeted delivery, potential for enhanced photothermal therapy, and reduced toxicity | May have potential for immune response and limited stability | Potentially high immunogenicity, but dependent on the specific lipid and mRNA target | Highly dependent on cancer target and delivery method | Generally safe, but potential for toxicity and adverse immune responses | Susceptible to degradation and require specialized storage conditions | [464] |
Polyplexes (e.g., polyethyleneimine, chitosan) | High transfection efficiency and low toxicity | May have potential for immune response and limited stability | Potentially high immunogenicity, but dependent on the specific polyplex and mRNA target | Highly dependent on cancer target and delivery method | Generally safe, but potential for toxicity and adverse immune responses | Susceptible to degradation and require specialized storage conditions | [448] |
Virus-like particles (VLPs) | High immunogenicity and antigenicity, potential for multivalent display of antigens | May have potential for immune response and limited stability | Highly dependent on the specific VLP and mRNA target | Highly dependent on cancer target and delivery method | Generally safe, but potential for toxicity and adverse immune responses | Susceptible to degradation and require specialized storage conditions | [295] |
Inorganic nanoparticles (e.g., calcium phosphate, zinc oxide) | High stability and biocompatibility, potential for targeted delivery | May have potential for immune response and limited efficacy | Potentially high immunogenicity, but dependent on the specific nanoparticle and mRNA target | Highly dependent on cancer target and delivery method | Generally safe, but potential for toxicity and adverse immune responses | Susceptible to degradation and require specialized storage conditions | [465] |
Cell-penetrating peptides | High transfection efficiency and low toxicity | Limited potential for targeted delivery and potential for immune response | Potentially high immunogenicity, but dependent on the specific peptide and mRNA target | Highly dependent on cancer target and delivery method | Generally safe, but potential for toxicity and adverse immune responses | Susceptible to degradation and require specialized storage conditions | [451] |
PEGylated lipid nanoparticles | Improved delivery efficiency and circulation time, reduced toxicity | Potential for immunogenicity and limited specificity | Potentially high immunogenicity, but dependent on the specific formulation and mRNA target | Highly dependent on cancer target and delivery method | Generally safe, but potential for toxicity and adverse immune responses | Susceptible to degradation and require specialized storage conditions | [466] |
Magnetofection | Targeted delivery and potential for enhanced efficacy | Limited potential for immune response, potential for toxicity and adverse immune responses | Potentially low immunogenicity, but dependent on the specific method and mRNA target | Highly dependent on cancer target and delivery method | Generally safe, but potential for toxicity and adverse immune responses | Susceptible to degradation and require specialized storage conditions | [438] |
mRNA-loaded extracellular vesicles | High stability and biocompatibility, potential for targeted delivery and sustained release | Limited potential for immune response, low transfection efficiency | Potentially low immunogenicity, but dependent on the specific vesicle and mRNA target | Highly dependent on cancer target and delivery method | Generally safe, but potential for toxicity and adverse immune responses | Susceptible to degradation and require specialized storage conditions | [467] |
CRISPR-Cas9 system | Highly targeted delivery and potential for gene editing | Potential for off-target effects, limited specificity and efficiency | Potentially high immunogenicity, but dependent on the specific system and mRNA target | Highly dependent on cancer target and delivery method | Potential for toxicity and adverse immune responses | Susceptible to degradation and require specialized storage conditions | [468] |
mRNA-protein conjugates | Enhanced immunogenicity and stability, potential for multivalent display of antigens | Limited potential for targeted delivery, low transfection efficiency | Potentially high immunogenicity, but dependent on the specific conjugate and mRNA target | Highly dependent on cancer target and delivery method | Generally safe, but potential for toxicity and adverse immune responses | Susceptible to degradation and require specialized storage conditions | [149] |
Dendrimer-based delivery systems | High transfection efficiency, improved stability and biocompatibility, and potential for targeted delivery | Potential for immune response, limited specificity, and potential for toxicity and adverse immune responses | Potentially high immunogenicity, but dependent on the specific dendrimer and mRNA target | Highly dependent on cancer target and delivery method | Generally safe, but potential for toxicity and adverse immune responses | Susceptible to degradation and require specialized storage conditions | [91] |
In-vivo electroporation | High transfection efficiency and potential for targeted delivery | Limited specificity, potential for immune response, and potential for toxicity and adverse immune responses | Potentially high immunogenicity, but dependent on the specific method and mRNA target | Highly dependent on cancer target and delivery method | Generally safe, but potential for toxicity and adverse immune responses | Susceptible to degradation and require specialized storage conditions | [453] |
Intra-lymphatic injection | Potential for targeted delivery and enhanced immune response | Limited potential for systemic effects, limited data on safety and efficacy | Potentially high immunogenicity, but dependent on the specific method and mRNA target | Highly dependent on cancer target and delivery method | Generally safe, but potential for toxicity and adverse immune responses | Susceptible to degradation and require specialized storage conditions | [61] |
Tumor-targeting aptamers | Potential for targeted delivery and reduced toxicity | Limited specificity and potential for immune response | Potentially high immunogenicity, but dependent on the specific aptamer and mRNA target | Highly dependent on cancer target and delivery method | Generally safe, but potential for toxicity and adverse immune responses | Susceptible to degradation and require specialized storage conditions | [469] |
Non-viral nanocarriers (e.g., carbon nanotubes, mesoporous silica nanoparticles) | High stability and potential for targeted delivery | Limited data on safety and efficacy, potential for toxicity and adverse immune responses | Potentially high immunogenicity, but dependent on the specific nanocarrier and mRNA target | Highly dependent on cancer target and delivery method | Generally safe, but potential for toxicity and adverse immune responses | Susceptible to degradation and require specialized storage conditions | [470] |