Table IV.
Receptor-Mediated Non-Viral Nucleic Acid Delivery to the Lung
| Receptor | Ligand | Delivery System | Type of nucleic acid |
Key results | Reference |
|---|---|---|---|---|---|
| Insulin receptor | Insulin | PEI polyplex | pDNA | Selective delivery to alveolar epithelial cells | [91] |
| Lactoferrin receptor | Lactoferrin | PEI polyplex | pDNA | Selective delivery to bronchial epithelial cells | [81] |
| Integrin | RGD motif | Liposome | pDNA | High transfection efficacy in lung endothelial cells for targeted liposomes in vivo | [54] |
| TAT-RGD motif | Direct conjugate | pDNA | Enhanced uptake of targeted particles by pulmonary cells | [176] | |
| Cationic liposome | pDNA | Fivefold increased gene expression in A549 cells compared to lipofectamine | |||
| RGD motif | Lipoplex | pDNA | Significantly improved transfection efficacy for RGD-bearing polyplexes | [177] | |
|
Polymeric IgR |
Antisecretory component antibody | PLL polyplex | pDNA | Proof of concept for transfection efficacy to human tracheal epithelial cells, competition assay blocked uptake of targeted polyplexes | [178] |
| PECAM | Anti-PECAM antibody | PEI polyplex | pDNA | Enhanced gene transfer efficacy and reduced toxicity | [179] |
| Anti-PECAM antibody | LNP | mRNA | Enhanced protein expression in lung endothelial cells; reduced accumulation in hepatocytes | [84] | |
| Transferrin receptor | Transferrin | PEI polyplex | siRNA | Enhanced uptake of Tf-PEI polyplexes by pulmonary ATCs in vitro and in asthma mouse model after intratracheal application; improved endosomal escape by addition of melittin, 40% more effective than lipofectamine | [180, 181] |
| β2-adrenoceptor | Clenbuterol | PEI polyplex | pDNA | Enhanced gene expression in alveolar epithelial cells | [50] |
| Salbutamol | Chitosan polyplex | siRNA | Delivery to bronchial epithelial cells | [51] | |
| IP1 | Iloprost and Treprostinil | PEI polyplex | pDNA | Enhanced transfection efficacy | [52] |
| Lectins |
Galactose Glucose Lactose |
PLL polyplex | pDNA | Improved, sugar-type dependent gene expression in cystic fibrosis airway epithelial cells | [185-188] |
| Galactose | PEGylated PEI polyplex | pDNA | Increased transfection efficacy in vitro and in vivo | [189] |
Abbreviations: PEI, polyethylene imine; RGD, arginine-glycine-aspartic acid; TAT, transactivated transcription peptide; Ig, immunoglobulin receptor; PLL, poly-L-lysine; PECAM, platelet endothelial cell adhesion molecule; IP1, prostacyclin receptor; PEI, polyethylene imine