From: The use of RNA-based treatments in the field of cancer immunotherapy
Delivery Method | Description | Mechanism of Action | Advantages | Disadvantages | Safety Concerns | Clinical Development Status | Potential Applications | Reference |
---|---|---|---|---|---|---|---|---|
In vivo injection of naked mRNA | Direct injection of mRNA into the patient | Expression of the antigen by host cells | Simple and low cost | Low transfection efficiency and immunogenicity | Inflammation at the injection site | Preclinical and early clinical trials | Melanoma, prostate cancer, infectious diseases | [61] |
Lipid nanoparticles (LNPs) | mRNA encapsulated in a lipid nanoparticle for delivery | Facilitate cellular uptake and mRNA release | High transfection efficiency and immunogenicity | Potential toxicity and accumulation in liver | Immune response to the lipid components | Clinical trials ongoing | Various cancer types, infectious diseases | [128] |
Electroporation | Electrical pulse applied to cells to increase permeability | Enhance mRNA delivery and uptake | High transfection efficiency and immunogenicity | Pain and muscle contractions | Electrode burn and tissue damage | Early clinical trials | Melanoma, breast cancer, head and neck cancer | [129] |
Dendritic cell loading | mRNA loaded into dendritic cells (DCs) for antigen presentation | Increase antigen presentation and T cell activation | Efficient and targeted delivery | Complex and costly production process | DC maturation and activation | Preclinical and early clinical trials | Various cancer types | [130] |
Polymeric nanoparticles | mRNA encapsulated in a polymeric nanoparticle for delivery | Facilitate cellular uptake and mRNA release | Biodegradable and biocompatible | Lower transfection efficiency than LNPs | Potential toxicity and accumulation in liver | Preclinical trials | Various cancer types, infectious diseases | [131] |
Protamine-condensed mRNA | mRNA condensed with protamine for delivery | Facilitate cellular uptake and mRNA release | Efficient and low cost | High toxicity and immunogenicity | Non-specific activation of immune cells | Preclinical trials | Various cancer types, infectious diseases | [132] |
mRNA-coated gold nanoparticles | mRNA adsorbed onto gold nanoparticles for delivery | Facilitate cellular uptake and mRNA release | Efficient and targeted delivery | Potential toxicity and accumulation in liver | Gold nanoparticles may activate immune cells | Preclinical trials | Various cancer types, infectious diseases | [133] |
In vitro transcribed mRNA-loaded exosomes | mRNA loaded into exosomes for delivery | Facilitate cellular uptake and mRNA release | Targeted delivery and high stability | Lower transfection efficiency than LNPs | Immunogenicity of the exosomes | Preclinical trials | Various cancer types | [66] |
Synthetic polymeric vectors | mRNA encapsulated in a synthetic polymeric vector for delivery | Facilitate cellular uptake and mRNA release | Biocompatible and biodegradable | Lower transfection efficiency than LNPs | Potential toxicity and accumulation in liver | Preclinical trials | Various cancer types | [134] |
Self-amplifying mRNA vaccines | mRNA encoding self-replicating RNA for delivery | Amplification of mRNA expression in vivo | High immunogenicity and long-term antigen expression | Potential toxicity and long-term safety concerns | Immune response to the viral components | Early clinical trials | Various cancer types | [2] |
mRNA-carrying oncolytic viruses | mRNA loaded into oncolytic viruses for delivery | Selective replication in cancer cells and antigen presentation | Tumor-specific delivery and amplification of mRNA expression | Potential toxicity and systemic spread | Immune response to the viral components | Preclinical trials | Various cancer types | [135] |
mRNA-nanocomplexes | mRNA encapsulated in a nanoparticle for delivery | Facilitate cellular uptake and mRNA release | Efficient and targeted delivery | Potential toxicity and accumulation in liver | Immune response to the delivery vehicle | Preclinical trials | Various cancer types | [136] |
mRNA-loaded hydrogels | mRNA embedded in a hydrogel matrix for delivery | Facilitate cellular uptake and mRNA release | Sustained release and targeted delivery | Lower transfection efficiency than LNPs | Inflammation and fibrosis at the injection site | Preclinical trials | Various cancer types | [2] |
mRNA-loaded microneedles | mRNA coated on microneedles for dermal delivery | Facilitate cellular uptake and mRNA release | Simple and painless administration | Limited to dermal applications | Risk of skin irritation and infection | Preclinical trials | Various cancer types, infectious diseases | [137] |
mRNA-electrospun fibers | mRNA encapsulated in electrospun fibers for delivery | Facilitate cellular uptake and mRNA release | Sustained release and targeted delivery | Limited to topical applications | Biocompatibility and toxicity concerns | Preclinical trials | Various cancer types, infectious diseases | [138] |
mRNA delivery via ultrasound-targeted microbubble destruction | mRNA delivered to the site of interest using ultrasound and microbubbles | Increased cellular uptake and gene expression at the site of interest | Targeted delivery, non-invasive | Limited to superficial tumors, small area of effect | Safety of microbubbles | Preclinical trials | Various cancer types | [139] |
mRNA delivery via magnetofection | mRNA complexed with magnetic particles and delivered using a magnetic field | Enhanced cellular uptake and transfection | Targeted delivery, non-invasive | Limited to superficial tumors, small area of effect | Safety of magnetic particles | Preclinical trials | Various cancer types | [140] |
mRNA delivery via nanoparticles with tumor-penetrating peptides | mRNA encapsulated in nanoparticles functionalized with tumor-penetrating peptides | Facilitates the penetration of mRNA-containing nanoparticles into tumor tissue | Enhanced tumor-targeting, high transfection efficiency | Limited to solid tumors | Safety of nanoparticles | Preclinical trials | Solid tumors | [141] |
mRNA delivery via bacterial vectors | mRNA loaded into attenuated bacteria and delivered to tumor site | Amplifies antigen presentation and tumor-specific immune response | Enhanced immunogenicity, targeted delivery | Potential for bacterial infection and immune response | Safety of bacterial vectors | Preclinical trials | Various cancer types | [142] |
mRNA delivery via hyaluronan nanogels | mRNA encapsulated in hyaluronan-based nanogels and delivered to the site of interest | Increased cellular uptake and transfection at the site of interest | Targeted delivery, non-toxic | Limited to superficial tumors, small area of effect | Safety of nanogels | Preclinical trials | Various cancer types | [143] |
mRNA delivery via bioresponsive polymeric nanoparticles | mRNA encapsulated in polymeric nanoparticles designed to degrade in response to specific stimuli | Facilitates site-specific mRNA delivery | Targeted delivery, non-toxic | Limited to tumors that can be targeted by specific stimuli | Safety of nanoparticles | Preclinical trials | Various cancer types | [144] |
mRNA delivery via tissue engineering scaffolds | mRNA incorporated into tissue engineering scaffolds and delivered to the site of interest | Enhanced cellular uptake and transfection at the site of interest | Site-specific delivery, potentially long-term antigen expression | Limited to solid tumors and tissue-engineered sites | Safety of scaffolds | Preclinical trials | Various cancer types, tissue engineering | [145] |
mRNA delivery via extracellular vesicles | mRNA encapsulated in extracellular vesicles derived from a patient's own cells and delivered to the site of interest | Enhanced tumor-targeting, high transfection efficiency | Targeted delivery, non-toxic | Limited to solid tumors | Safety of extracellular vesicles | Preclinical trials | Solid tumors | [146] |
mRNA delivery via in vivo electroporation | mRNA delivered to tissue via electroporation | Facilitates cellular uptake and gene expression | Targeted delivery, non-toxic | Limited to specific tissue types and requires specialized equipment | Risk of tissue damage from electroporation | Preclinical trials, some clinical trials | Various cancer types | [147] |
mRNA delivery via dissolvable microneedle arrays | mRNA coated onto dissolvable microneedles and applied to skin | Facilitates cellular uptake and gene expression in skin | Targeted delivery, non-invasive | Limited to skin and superficial tumors | Safety of microneedles | Preclinical trials | Skin cancers | [148] |
mRNA delivery via laser ablation | mRNA delivered to tissue via laser ablation | Facilitates cellular uptake and gene expression | Targeted delivery, non-toxic | Limited to specific tissue types and requires specialized equipment | Risk of tissue damage from laser ablation | Preclinical trials | Various cancer types | [149] |
mRNA delivery via microfluidic chips | mRNA delivered to cells via microfluidic chips | Facilitates cellular uptake and gene expression | Targeted delivery, precise control over flow rates and concentrations | Limited to specific cell types and requires specialized equipment | Safety of microfluidic chips | Preclinical trials | Various cancer types | [150] |
mRNA delivery via electrospray | mRNA delivered to tissue via electrospray | Facilitates cellular uptake and gene expression | Targeted delivery, non-toxic | Limited to specific tissue types and requires specialized equipment | Safety of electrospray | Preclinical trials | Various cancer types | [151] |
mRNA delivery via cell-penetrating peptides | mRNA complexed with cell-penetrating peptides and delivered to cells | Facilitates cellular uptake and gene expression | Targeted delivery, non-toxic | Limited to specific cell types | Safety of cell-penetrating peptides | Preclinical trials | Various cancer types | [152] |
mRNA delivery via gene gun | mRNA coated onto gold particles and delivered to tissue via gene gun | Facilitates cellular uptake and gene expression | Targeted delivery, non-toxic | Limited to specific tissue types and requires specialized equipment | Risk of tissue damage from gene gun | Preclinical trials | Various cancer types | [153] |
mRNA delivery via polymeric carriers | mRNA complexed with biodegradable polymeric carriers and delivered to tissue | Facilitates cellular uptake and gene expression | Targeted delivery, non-toxic, controlled release | Limited to specific tissue types and requires specialized equipment | Safety of polymeric carriers | Preclinical trials | Various cancer types | [154] |
mRNA delivery via lipoplexes | mRNA complexed with lipids and delivered to cells | Facilitates cellular uptake and gene expression | Non-toxic, efficient | Limited to specific cell types | Safety of lipids | Preclinical trials | Various cancer types | [155] |
mRNA delivery via dendrimers | mRNA complexed with dendrimers and delivered to cells | Facilitates cellular uptake and gene expression | Non-toxic, efficient | Limited to specific cell types | Safety of dendrimers | Preclinical trials | Various cancer types | [156] |
mRNA delivery via gold nanoparticles | mRNA complexed with gold nanoparticles and delivered to cells | Facilitates cellular uptake and gene expression | Non-toxic, efficient | Limited to specific cell types | Safety of gold nanoparticles | Preclinical trials | Various cancer types | [133] |
mRNA delivery via viral vectors | mRNA loaded into viral vectors and delivered to cells | Facilitates cellular uptake and gene expression | High transfection efficiency, targeted delivery | Risk of immune response and viral integration | Safety of viral vectors | Preclinical trials | Various cancer types | [157] |
mRNA delivery via cell-based vehicles | mRNA loaded into various cell types and delivered to target tissues | Facilitates cellular uptake and gene expression | Non-toxic, potential for targeting and controlled release | Limited to specific cell types and requires specialized equipment | Safety of cell-based vehicles | Preclinical trials | Various cancer types | [158] |
mRNA delivery via exosomes | mRNA encapsulated in exosomes and delivered to target tissues | Facilitates cellular uptake and gene expression | Non-toxic, potential for targeting and controlled release | Limited to specific tissues | Safety of exosomes | Preclinical trials | Various cancer types | [159] |
mRNA delivery via ribonucleoprotein complexes | mRNA complexed with ribonucleoproteins and delivered to cells | Facilitates cellular uptake and gene expression | Non-toxic, efficient | Limited to specific cell types | Safety of ribonucleoproteins | Preclinical trials | Various cancer types | [147] |
mRNA delivery via inorganic nanoparticles | mRNA complexed with inorganic nanoparticles and delivered to cells | Facilitates cellular uptake and gene expression | Non-toxic, efficient, targeted delivery | Limited to specific cell types | Safety of inorganic nanoparticles | Preclinical trials | Various cancer types | [147] |
mRNA delivery via sonoporation | mRNA delivered to tissue via ultrasound-mediated sonoporation | Facilitates cellular uptake and gene expression | Non-invasive, targeted delivery | Limited to specific tissue types and requires specialized equipment | Risk of tissue damage from sonoporation | Preclinical trials | Various cancer types | [160] |
mRNA delivery via gas-filled microbubbles | mRNA delivered to tissue via microbubble-assisted ultrasound | Facilitates cellular uptake and gene expression | Non-invasive, targeted delivery | Limited to specific tissue types and requires specialized equipment | Safety of microbubbles | Preclinical trials | Various cancer types | [161] |
mRNA delivery via electrical fields | mRNA delivered to cells via electrical fields | Facilitates cellular uptake and gene expression | Non-toxic, efficient | Limited to specific cell types and requires specialized equipment | Safety of electrical fields | Preclinical trials | Various cancer types | [162] |
mRNA delivery via bacterial vectors | mRNA loaded into bacterial vectors and delivered to cells | Facilitates cellular uptake and gene expression | Targeted delivery, high transfection efficiency | Risk of immune response and bacterial infection | Safety of bacterial vectors | Preclinical trials | Various cancer types | [147] |
mRNA delivery via CRISPR-Cas systems | mRNA encoding CRISPR-Cas system delivered to cells | Facilitates targeted gene editing | Precise, efficient | Limited to specific cell types and requires specialized equipment | Safety of CRISPR-Cas system | Preclinical trials | Various cancer types | [163] |
mRNA delivery via cell-penetrating antibodies | mRNA complexed with cell-penetrating antibodies and delivered to cells | Facilitates cellular uptake and gene expression | Non-toxic, potential for targeting and controlled release | Limited to specific cell types | Safety of cell-penetrating antibodies | Preclinical trials | Various cancer types | [164] |
mRNA delivery via non-viral vectors | mRNA complexed with non-viral vectors and delivered to cells | Facilitates cellular uptake and gene expression | Non-toxic, efficient, potential for targeted delivery | Limited to specific cell types | Safety of non-viral vectors | Preclinical trials | Various cancer types | [165] |