Representative nanoparticulate drug delivery systems for nucleic acid therapeutics. (A) Delivery of nucleic acid therapeutics using micelles comprise of amphiphilic molecules, such as amphiphilic block polymers. Micelles contain hydrophilic regions as well as hydrophobic regions. After reaching the critical micelle concentration, micelles can be formed with nucleic acid loading in hydrophilic side via mechanisms such as electrostatic interactions or Van der Waals interactions. (B) Delivery of nucleic acid therapeutics using polymer nanoparticles that can load nucleic acids through various mechanism, most commonly using cationic polymers, which can form nanoparticles with negative nucleic acid via electrostatic interactions. (C) Delivery of nucleic acid therapeutics using lipid nanoparticles comprise of lipids such as lecithin, DOPC, and DSPE. Polyethylene glycol (PEG) modification of lipids enhance the half-life of lipid nanoparticles. DOPC: 1,2-dioleoyl-sn-glycero-3-phosphocholine; DSPE: 1,2-distearoyl-sn-glycero-3-phosphorylethanolamine. (D) Delivery of nucleic acid therapeutics using lipid calcium phosphate (CaP) nanoparticles. CaP encapsulates nucleic acids due to the co-precipitation of the phosphate on nucleic acid backbones with calcium-phosphate. Lipids make CaP nanoparticles more stable and can facilitate cellular delivery.