Table 3.
Overview of delivery systems for miRNAs therapeutics and the effects of their modulation in PDAC
| Delivery system | Target | Type study | Effects of modulation of miR | Model | Ref. |
|---|---|---|---|---|---|
| PEGylated tandem peptide pTP-iRGD | miR-21 | In vitro In vivo | Reduction of PDO size and viability and sensitizing resistant PDOs to gemcitabine Tumor growth suppression of PDX models | Patient-derived-organoid (PDO) of HPDE6c7 epithelial ductal pancreatic cells and PDAC human and mouse cell lines (PANC-1 and D8-175) | [73] |
| EPOPC:Chol cationic liposomes | miR-21 | In vitro | Significant increase in downstream target PTEN, synergistic antitumor effect when combined with sunitinib malate | PDAC cells Hs766T, and normal pancreatic ductal cells HPNE | [74] |
| EPOPC:Chol cationic liposomes | miR-10b | In vitro | Significant increase in downstream target HoxD10 | PDAC cells Hs766T, and normal pancreatic ductal cells HPNE | [74] |
| EPOPC:Chol cationic liposomes | miR-221 and miR-222 | In vitro | Significant increase in downstream target
|
PDAC cells Hs766T, and normal pancreatic ductal cells HPNE | [74] |
| Lentiviral vectors | miR-21 | In vivo | Inhibition of proliferation and apoptosis leading to suppressed tumor growth | PDAC Capan-2, MiaPaCa-2 cells and xenograft mouse models | [75] |
| Nano particles of cationic amphiphile (DOTAP) and co-lipids | miR-34a | In vivo | Enhanced intra-tumoral apoptosis and growth inhibition of subcutaneous cancer xenografts. | MiaPaCa-2 cells and CD-1 athymic nu/nu mice as xenograft models | [76] |
| Nanoparticles of cationic amphi-phile (DOTAP) and co-lipids | miR-143/145 cluster | In vivo | Enhanced intra-tumoral apoptosis and growth inhibition of subcutaneous cancer xenografts. | MiaPaCa-2 cells and CD-1 athymic nu/nu mice as xenograft models | [76] |
| Liposomal miR-34a mimic (MXR-34) | miR-34a | Phase I trial | Some antitumoral activity accompanied with tolerated AEs such as fatigue and fever. | Patients aged ≥ 18 years and with refractory solid tumors for which no standard treatment existed | [77] |
| Exosomes | miR-34a | In vitro | downregulation of miR-34a target gene Bcl-2 and inhibition of pancreatic cells | Normal human pancreatic epithelial ductal cells HPDE6c7, and human PDAC MIA PaCa-2 and Panc28 cell lines | [78] |
| Exosomes | miR-34a | In vivo | Inhibition of growth of orthotopic PDAC xenografts | Subcutaneous xenograft of Panc28 cells in nude BALB/c mice | [78] |