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Table 5 The different types of physical delivery methods for mRNA cancer vaccines

From: The use of RNA-based treatments in the field of cancer immunotherapy

Delivery Method

Advantages

Disadvantages

Immunogenicity

Efficacy

Safety

Stability

Reference

Electroporation (EP)

Enhances uptake and expression of mRNA, can be used with a variety of tissues

Can cause discomfort and pain, may damage surrounding tissue or cells

High

High

Moderate

Unstable

[228]

Sonoporation

Non-invasive, highly specific targeting, can be used with a variety of tissues

Limited penetration depth, requires specialized equipment

Moderate

High

High

Stable

[433]

Laser microporation

Precise and controlled delivery, can be used with a variety of tissues

Limited scale-up capabilities, may require specialized equipment or expertise

High

High

High

Stable

[434]

Jet injection

Rapid and efficient delivery, can be used with a variety of tissues

May cause inflammation or tissue damage, limited depth of penetration

High

Moderate

Moderate

Stable

[435]

Needle-free injection

Non-invasive, easy to use

Limited depth of penetration, may cause tissue damage or inflammation

Moderate

Moderate

High

Stable

[436]

Gold particle bombardment

Can deliver to specific cells, easy to use

Limited scale-up capabilities, may cause tissue damage or inflammation

High

Moderate

Moderate

Stable

[437]

Magnetofection

Can deliver to specific cells or tissues, non-invasive

Limited depth of penetration, may require specialized equipment or expertise

High

High

High

Stable

[438]

Microprojection array

Precise and controlled delivery, can be used with a variety of tissues

Limited scale-up capabilities, may cause tissue damage or inflammation

High

High

High

Stable

[439]

Biodegradable nanoparticle

Targeted delivery, can be used with a variety of tissues

Requires optimization of size and charge for effective delivery, possible toxicity

High

High

High

Stable

[440]

Hyaluronic acid-based nanoparticle

Targeted delivery, can be used with a variety of tissues

Requires optimization of size and charge for effective delivery, limited scale-up capabilities

High

High

High

Stable

[143]

Cell-penetrating peptide

Efficient delivery to cells and tissues, low toxicity

Limited stability, may cause inflammation or tissue damage

High

Moderate

Moderate

Unstable

[441]

Hydrodynamic delivery

Rapid and efficient delivery, can be used with a variety of tissues

Limited depth of penetration, can cause tissue damage

High

High

High

Unstable

[442]

Ultrasound-mediated delivery

Non-invasive, can target specific cells and tissues

Limited depth of penetration, may require specialized equipment or expertise

Moderate

High

High

Stable

[160]

Viral vector-mediated delivery

High transfection efficiency, can be used with a variety of tissues

Limited scale-up capabilities, potential for immune response or toxicity

High

High

Low

Stable

[443]

Liposome-mediated delivery

Targeted delivery, low toxicity, easy to prepare

Limited scale-up capabilities, may cause inflammation or tissue damage

Moderate

Moderate

High

Stable

[198]

Calcium phosphate nanoparticle

Efficient delivery to cells and tissues, low toxicity

Limited scale-up capabilities, may cause inflammation or tissue damage

High

High

High

Stable

[444]

Magnet-assisted transfection (MAT)

Non-invasive, can target specific cells and tissues, low toxicity

Limited depth of penetration, requires specialized equipment

High

High

High

Stable

[445]

Photochemical internalization (PCI)

Targeted delivery, low toxicity, can enhance immunogenicity

Limited scale-up capabilities, requires specialized equipment

High

High

High

Stable

[446]

Cyclic dinucleotide-based delivery

Can enhance immune response, low toxicity

Limited scale-up capabilities, may cause inflammation or tissue damage

High

Moderate

Moderate

Stable

[447]

Nanoparticles with antigen presenting cells (APCs)

Efficient delivery to APCs, can enhance immune response

Requires optimization of size and charge for effective delivery, limited scale-up capabilities

High

High

High

Stable

[448]

Gene gun delivery

Precise and controlled delivery, can be used with a variety of tissues

Limited scale-up capabilities, may cause tissue damage or inflammation

High

High

High

Stable

[437]

Inorganic nanoparticle-mediated delivery

Targeted delivery, high loading capacity

Limited scale-up capabilities, requires optimization of size and charge for effective delivery

High

High

High

Stable

[449]

Topical delivery

Non-invasive, easy to use

Limited depth of penetration, may cause skin irritation or inflammation

Moderate

Moderate

High

Stable

[450]

Inhalation delivery

Non-invasive, can target specific cells and tissues in the respiratory tract

Limited depth of penetration, may cause respiratory irritation or inflammation

Moderate

Moderate

High

Stable

[451]

Acoustofluidic delivery

Non-invasive, can be used with a variety of tissues, can achieve high transfection efficiency

Requires specialized equipment, limited scale-up capabilities

High

High

High

Stable

[452]

In vivo electroporation

Efficient delivery, can be used with a variety of tissues

Can cause tissue damage, may require specialized equipment or expertise

High

High

High

Stable

[453]

Nanoparticle-laden microbubbles

Non-invasive, can achieve high transfection efficiency

Limited scale-up capabilities, requires specialized equipment

High

High

High

Stable

[454]

Supramolecular nanostructures

Targeted delivery, high loading capacity, can be used with a variety of tissues

Requires optimization of size and charge for effective delivery, limited scale-up capabilities

High

High

High

Stable

[455]

Magnetic field-guided delivery

Precise and controlled delivery, non-invasive

Limited depth of penetration, requires specialized equipment

High

High

High

Stable

[456]

Polymer-based microneedles

Non-invasive, easy to use

Limited depth of penetration, requires specialized equipment or expertise

Moderate

Moderate

High

Stable

[457]

Gold nanorod-mediated delivery

Targeted delivery, can achieve high transfection efficiency

Limited scale-up capabilities, requires optimization of size and charge for effective delivery

High

High

High

Stable

[458]

Dendritic cell-mediated delivery

Efficient delivery to dendritic cells, can enhance immune response

Requires specialized equipment or expertise, limited scale-up capabilities

High

High

High

Stable

[72]

Cell-penetrating peptides (CPPs)

Non-invasive, can be used with a variety of tissues

Limited scale-up capabilities, may have low transfection efficiency

Moderate

Moderate

High

Stable

[459]

Ultrasound-mediated delivery

Non-invasive, can achieve high transfection efficiency

Limited scale-up capabilities, requires specialized equipment

High

High

High

Stable

[460]

Bioreducible lipid nanoparticles

Targeted delivery, can enhance immune response, can achieve high transfection efficiency

Requires optimization of size and charge for effective delivery, limited scale-up capabilities

High

High

High

Stable

[424]

Surface-modified nanoparticles

Targeted delivery, can enhance immune response, can achieve high transfection efficiency

Requires optimization of size and charge for effective delivery, limited scale-up capabilities

High

High

High

Stable

[461]

Viral vectors (e.g. adenovirus, lentivirus)

Efficient delivery, high transfection efficiency

Safety concerns (e.g., integration, immunogenicity), limited scale-up capabilities, complex manufacturing

High

High

Variable

Stable

[344]

Cell-based delivery

Efficient delivery, can enhance immune response

Requires specialized equipment or expertise, may have limited scale-up capabilities, safety concerns (e.g., tumorigenicity)

High

High

Variable

Stable

[462]