Table 1

Comparison of various nanocarriers for miRNA-based therapy

Delivery system	Advantage	Disadvantage	Ref.
Lipid-based systems
Cationic lipids	High transfection efficacy, reduced rate of phagocytic clearance, easy large-scale production	Accumulation of particles in liver, spleen and lung, interferon response induction, possible elimination by mononuclear phagocyte system	^65–67
Neutral lipids	Less cytotoxic effects, non-immunogenic, non-phagocytic elimination	Low loading capacity and transfection efficacy for miRNAs, hardly endocytosed by cells	^68–70
Ionizable lipids	Limited side effects, non-immunogenic, longer circulating time	Low loading capacity	^65,71
Polymer-based systems
Chitosans	pH tunable drug releasing system, low immunogenicity, mucoadhesive and antibacterial potential	Poor stability, less solubility, low transfection efficacy and lack of control over pore-size property	^72,73
Dendrimers	Good stability, easily modified at the surface	Hemolytic activity, uncontrolled release of drug	^74,75
PLGAs^a	Biocompatibility, controllable release of drug, prolonged residence time in vital organs	Poor drug loading, high production costs, difficult to scale-up	^76–78
PEIs^b	High buffering and loading capacities	Toxicity, poor biodegradable polymer	^79,80
Poly lysines	Slow degradation and gradually release of drugs	High charge density, toxicity	^81–83
Protamines	Improves delivery of siRNAs	Associated with some side effects such as pulmonary hypertension and anaphylactic	^84,85
CPPs^c	Easy preparation, reserving biological activity of cargo, low cytotoxicity	Heterogeneity of the nanoparticle, interaction with plasma protein, low in vivo efficacy	^82,86,87
R3V6	Transportation of small RNAs more effective than PEI and lipofectamine	-	^88,89
Atelocollage	Reduced cargo immunogenicity, high transfection efficiency	Possible immunogenicity	^90–92
Inorganic nanoparticles
Golden nanoparticles	Easily modified at the surface, high stability, non-immunogenic, controllable drug loading and release deep inside tissues	Less drug loading capacity	^93,94
MSNs^d	Non-toxicity, high drug loading capability, easily modified at the surface, tunable pore structures, releasing agents in response to specific signals	Production and reproducibility problems in large scales	⁹⁵
IONPs^e	Easy preparation, biocompatible, low toxicity, high stability	Very long circulation time	⁹⁶
QDs^f	Strong adsorption capacity, more reactivity activity, smaller size	Immune response induction when using heavy metals for preparation of QDs	^97–100
GOs^g	Antibacterial properties, low toxicity, easier translocation across the membrane	Require more studies to prove the biocompatibility of GO in vivo	^101,102
NFs^h	Low cost, controlled releasing of drug over a definite period, more feasibility to load miRNAs for long-term delivery application	Limited control on pore size of particles, become brittleness after calcination	^103–107
Folate	Quickly taken up by cancer cells, easier penetration of miRNA to dense extracellular matrix in solid tumors		¹⁰⁸
Nucleic acid-based delivery systems
Aptamers	High safety, high binding affinity to target cells	Easy degradation by blood nuclease, difficulties in conjugating with some therapeutic agent	^109,110
pRNAⁱ	High solubility and stability, long half-life		^111–113

^aPoly(lactic-co-glycolic acid); ^bpolyethyleneimines; ^ccell-penetrating peptides; ^dmesoporous silica nanoparticles; ^eiron oxide nanoparticles; ^fquantum dots; ^ggraphene oxide; ^hnanofibers; ⁱpackaging RNA.