Table 5.
Examples of NPs and methods used for RNAs loading.
| Method of Incorporation | Type of RNA | Nanocarriers components | Encapsulation efficiency | Reference |
|---|---|---|---|---|
| Electrostatic Adsorption | siRNA | Branched PEI 25 kDa | Complexed with siRNA above the N/P ratio of 2.5 | [38] |
| siRNA | Linear PEI | N/P ratio of 5 | [39] | |
| siRNA | BPAE-SS | ~100% at polymer/siRNA weight ratios higher than 10 | [40] | |
| siRNA | ABP | ∼95% condensation of siRNA at ABP/siRNA weight ratios of greater than 1.5 | [41] | |
| siRNA | PLGA-PEI | Encapsulation efficiency of 81 ± 2%, loading siRNA of 198 ± 5 μg/30 mg | [42] | |
| siRNA | CS, γ-PGA | CS/siRNA complexes at N/P ratios ranging from 50/1 to 200/1; CS/siRNA/γ-PGA complexes at N/P/C ratio ranging from 100/1/0 to 100/1/50 | [43] | |
| miRNA | PCL-PEI, PCL-PEG | Efficiently condense miRNA at an N:P ratio of 8:1 | [44] | |
| siRNA | PAMAM dendrimers G7 (Gn (n: dendrimer generation number)) | Completely entrap siRNA at N/P ratios >2.5 | [45] | |
| siRNA | Amphiphilic PAMAM dendrimers G5 bearing different alkyl chain length and dendron size | Only the combined effect of the hydrophobic alkyl chain and the cationic hydrophilic PAMAM dendron was able to complexed with siRNA completely at N/P ratios over 2.5 | [46] | |
| siRNA | PCL-g-PDMAEMA, PGA-g-mPEG (or PGA-g-PEG-folate) | Totally encapsulated even at N/P = 3:1 | [47] | |
| siRNA | PAMAM-PEG-PLL | Complexed completely with siRNA at the N/P ratio of 1 and above | [48] | |
| siRNA | Cationic lipid DC-6-14, cholesterol, dioleoylphosphatidylethanolamine, vitamin A | Entrapment efficiencies were 95.6 ± 3.0% | [49] | |
| siRNA | Cationic lipid RPR209120 (2-(3-[Bis-(3-amino-propyl)-amino]-propylamino)-N-ditetradecylcarbamoylme-thyl-acetamide), 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine (DOPE), | 6 nmoles of RPR209120/μg siRNA | [50] | |
| siRNA | DOTAP | The DOTAP siRNA ratio was 2:1 (vol/wt) | [51,52], | |
| miRNA | mPEG-PLGA-PLL | encapsulation efficiency of 89.4% | [53] | |
| Core-shell encapsulation | siRNA | PEG-P(TMC-DTC)-PEI, cNGQ-PEG-P(TMC-DTC) | siRNA was completely loaded into the polymersomes at siRNA/polymer ratio of 80/100 (w/w) (N/P ratio of 0.45) | [54] |
| miRNA | G4 PAMAM, humanized Archaeoglobus ferritin (HumFt) | > 90% | [55] | |
| siRNA | Acrylate guanidine, N,N′-bis(acryloyl) cystamine containing disulfide bonds, polyethylene glycol with acylate and succinate functional end groups, Angiopep-2 (Ang) peptide | One nanocapsule with single siRNA inside | [56] | |
| siRNA | PCL-PEI, DOPE, cholesterol, DSPE-PEG | Encapsulation efficiency >98% at N/P = 5 | [57] | |
| siRNA | Cationic lipid-like compound (PEI-C12), PLGA, lecithin, DSPE-PEG, peptide H7K(R2)2 | Entrapment efficiency of 87.11 ± 1.79%, drug loading was 322.96 ± 6.66 pmol of siRNA per mg of H7K(R2)2-PSNPs | [58] | |
| siRNA | mPEG5K-PLA25K, BHEM-Chol | Encapsulation efficiency of siRNA could be above 90% and the siRNA loading weight ratio was up to 4.47% | [59] | |
| siRNA | Lanthanum phosphate, CS | Efficient encapsulation of siRNAs in CS/LaP/siRNA NPs and protection from enzymatic degradation in intestinal fluid up to 72 h | [60] | |
| siRNA | Bioreducible cholesterol-grafted poly(amidoamine) (rPAA-Chol polymer), DOTAP, DOPE, cholesterol, DSPE-PEG (or DSPE-PEG-T7) | – | [61] | |
| mRNA | PBAE polymer, EDOPC, DOPE, DSPE-PEG2000 | mRNA was fully encapsulated at PBAE/mRNA ratio (w/w) of 20 or beyond | [62] | |
| siRNA | PLGA, lecithin, cationic lipid G0-C14, DSPE-PEG5K | siRNA encapsulation efficiency at ∼80% and a loading of ∼640 pmol siRNA/mg PLGA | [63] | |
| mRNA | Cationic compound SW-01, ionizable lipid, DOPE, PEG-lipid | Encapsulation efficiency of ~100% remained consistent over a 6-week duration | [64] | |
| siRNA | Mesoporous silica nanoparticles (MSN), DOTAP, block copolymer 454 | siRNA loading capacities of up to 380 μg per mg MSN | [65] | |
| siRNA | PEG77-XPLG*LAGr9X–PCL17 | Complete siRNA binding at N/P ratio of 3:1 | [66] | |
| shRNA | Fe3O4 NPs, FITC-SiO2, PEI-FA | Completely complexed with shRNA at NPs/shRNA weight ratio of 15:1 | [67] | |
| Electrostatic interaction-based layer-by-layer encapsulation | siRNA | Se NPs, CS | – | [68] |
| siRNA | Au NPs, thiolated LPEI, PEGylated LPEI | Total siRNA loading at N/P 2 and above | [69] | |
| siRNA | carboxyl-modified polystyrene latex NPs (CML), poly-L-Arg | a single bilayer on the NP surface could load up to 3500 siRNAs | [70] | |
| mRNA | Dextran sulfate, poly-L-arginine, CaCO3 | loading efficiency of (39.9 ± 6.3)% | [71] | |
| shRNA | DOTAP, HA, CMO, HAase | – | [72] | |
| shRNA | Au-PEI, CS-Aco, PEI | Complete loading at (Au-PEI/CS-Aco/PEI)/shRNA mass ratio of 5/1 | [73] | |
| siRNA | PLGA, poly-L-Arg, HA-methyltetrazine conjugate, CD20 antibody | – | [74] | |
| siRNA | Au NPs, PEI, polymer SS37, polymer 447 | Encapsulation efficiency of ~94%–100%, layering efficiencies of 80 ± 3% | [75] | |
| siRNA | Au NPs, PLL | Total 4 layers of PLL and 3 layers of siRNA | [76] | |
| siRNA | Au NPs, 11-mercaptoundecanoic acid (MUA), PEI 25 kDa | Around 780 siRNA molecules per PEI/siRNA/PEI-AuNP | [77] | |
| miRNA | PLGA, PLL | Loading efficiency of 99%, such that 0.25 mg of PLGA NPs contained 10 nmoles miRNA | [78] | |
| miRNA | mesoporous titania NPs (MTNst), PLL, silica, PEG-block-poly-(l-aspartic acid) (PEG-b-PLD), paclitaxel (PTX) | miR708 was efficiently loaded at an N/P ratio of 2:1 | [79] | |
| Non-electrostatic interaction-based encapsulation | siRNA | CpG-g-PCL, siSTAT3 linker | Nearly 100% loading efficiency of siRNAs | [80] |
| siRNA | DNA tetrahedron with tails (tailed-TET) | The ratio of tailed-TET to siRNA linker at 1: 1.8 | [81] | |
| siRNA | DOX·HCl, PEG-b-PLA | Hydrophobic [siRNA&DOX] with an encapsulation efficacy of 41.16 ± 0.47% | [82] | |
| siRNA | Zinc(II)-bis(dipicolylamine) (Zn2BDPA) lipid derivatives with different fatty acids, GMO, pluronic F108 | Complexed with siRNA formed at Z/P ratio of 10 | [83] | |
| siRNA | DOPG, DOPE, calcium ions | 100% siRNA loading at Ca2+/siRNA molar charge ratio of 2.5/1 | [84] | |
| siRNA | Calcium phosphate, AHA | – | [85] | |
| miRNA | GOA prodrugs | The molar ratio of GOA/miR at 120:1 | [86] | |
| siRNA | Amphiphilic HA conjugate bearing 5β-cholanic acids and ZnII–dipicolylamine complexes (Zn–DPA) | 15 pmol siRNA was binded with 100 μg HADPA-Zn-NPs | [87] | |
| siRNA | PEG-b-poly(benzoxaborole) (PEG-PBO), calcium phosphate | The incorporation efficacy of siRNA was about 94% at the PEG-PBO to siRNA weight ratio of 20 | [88] | |
| siRNA | HA | – | [89] | |
| siRNA | Mesoporous silica NPs (MSNs), calcium ion | The siRNA loading capacity per MSN particle was estimated to be ∼1.25 pmol/μg | [90] | |
| AS1411 or single-stranded RNAs (122S) or antisense oligonucleotide (G3139) | Nucleobase-lipids DXBAs (DOTA, DNTA, DOCA or DNCA) | Unmodified and peptide-conjugated single-stranded oligonucleotides (including 122S, P122S, AS1411 and N-G3139) could be effectively encapsulated at a base ratio of 5:1 (>80%) | [91] |
Abbreviation: SS37: 1-(3-aminopropyl)-4-methylpiperazine end-modified poly(N,N′-bis(acryloyl)cystamine-co-3-amino-1-propanol), 447: 1-(3-aminopropyl)-4-methylpiperazine end-modified poly(1,4-butanediol diacrylate-co-4-amino-1-butanol), BPAE-SS: branched poly(β-amino ester)s containing disulfide linkages, PBAE: poly (β-amino ester), PEG-b-PLA: poly(ethylene glycol)-block-poly(D,l-lactide), DOPG: 1,2-dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol), PEI: polyethyleneimine, mPEG: methoxy poly (ethylene glycol), PLGA: Poly (lactic-co-glycolic acid), PCL: poly(ε-caprolactone), ABP: arginine grafted bioreducible poly (disulfide amine) polymer, γ-PGA: poly(γ-glutamic acid), PAMAM: polyamidoamine, PDMAEMA: poly(2-dimethylaminoethyl methacrylate), PLL: poly-l-lysine, poly-L-Arg: poly-L-arginine, CS: chitosan, CS-Aco: chitosan-aconitic anhydride, AHA: alendronate-hyaluronan graft polymer, GOA: gemcitabine-oleic acid prodrugs, GMO: glycerol monooleate, HA: hyaluronic acid, HAase: hyaluronidase, CMO: Chitosan with an oleic acid tail.