Table 2.

Advantages and disadvantages of nanosystems used for RNA delivery.

Nanosystems		Advantages	Disadvantages	References
Lipid-based nanosystems	Liposomes	-high biodegradability -cationic systems present high compaction efficiency	-cost-effectiveness -off-target effects -cytotoxicity of cationic systems	[43]
	SLN	-easy large-scale production -higher loading capacity than liposomes -high cargo bioavailability -controlled cargo release	-high toxicity when derived from cationic lipids -crystallization upon long-term storage -stability issues	[43,65,66]
	Exosomes	-low immunogenicity -high biocompatibility -high protection of nucleic acids -cell targeting capacity	-heterogeneity of natural matrix -limited large-scale production -limited transfection efficiency	[72]
Polymeric systems		-ease of synthesis and surface modification -versatility of structural conformations -biodegradability (in some cases through derivatization)	-non-degradable polymers tend to accumulate in tissues inducing cytotoxicity -in vivo metabolism and elimination routes still unknown	[134]
Inorganic nanoparticles	Metallic (Au, iron)	-variability in size, structure and geometry -ease of functionalization	-limited information concerning biocompatibility and cytotoxicity	[113,135,136]
	Carbon nanotubes	-possibilities of surface modification -low cytotoxicity and good biocompatibility of modified systems -high loading capacity	-limited in vivo studies developed	[115,116]
	Silica	-large surface area and thus an enhanced loading capacity -low toxicity	-not able to induce endosomal escape (must be chemically modified) -limited information about biocompatibility and biodistribution available	[124,125]