Table 1.
Ligand-targeted miRNA or siRNA delivery systems for cancer therapy
| Ligand/receptor | miRNA/siRNA | RNA chemical modification | Condition | Outcome | Ref. |
|---|---|---|---|---|---|
| Ligand-targeted (vehicle-free) delivery | |||||
| Folate/FR | miR-34a | 2′-O-Methyl nucleotides | Breast and lung cancer | Inhibition of tumor growth | (71) |
| Folate-nigericin/FR | miR-34a | 2′-O-Methyl nucleotides | Breast cancer | Downregulation of cell proliferation | (73) |
| Folate/FR | siLuciferase | 2′-O-Methyl nucleotides | Breast cancer | Downregulation of Luciferase activity | (71) |
| Folate-ODN/ FR | siαV integrin, siSurvivin | Unmodified | FR+ HUVECs/ KB cells | Significant downregulation of target genes | (69) |
| Folate/FR | siLuciferase, siBCL-2 | Unmodified * | FR+ HeLa cells | Significant downregulation of target genes | (70) |
| DUPA-dsRBD/ PSMA | siPLK1 | 2′-O-Methyl or 2′-F nucleotides, PS bonds | Prostate cancer | Inhibition of tumor growth | (43) |
| Trivalent DUPA/ PSMA | siPLK1 | 2′-O-Methyl nucleotides, PS bonds | Prostate cancer | Inhibition of tumor growth | (78) |
| GL21.T aptamer/ AXL receptor | let-7g | 2′-F pyrimidines | Lung cancer | Inhibition of tumor growth | (83) |
| GL21.T aptamer/ AXL receptor | miR-212 | 2′-F pyrimidines | Lung cancer | Sensitization of lung cancer to TRAIL therapy | (84) |
| GL21.T aptamer/ AXL receptor | miR-34c | 2′-F pyrimidines | Lung cancer | Synergistic inhibition of cell proliferation by GL21.T-miR-34c and erlotinib | (86) |
| GL21.T aptamer/ AXL receptor | miR-148b | 2′-F pyrimidines | Breast cancer and melanoma | Apoptosis and necrosis in breast tumor, prevented tumor cell dissemination | (87) |
| anti-KIT aptamer/ KIT receptor | miR-26a | 2′-F uridines | Basal-like breast cancer cells and HSPCs | Inhibition of tumor growth and protection against chemotherapy induced myelosuppression | (88) |
| apt69.T aptamer/ BCMA | miR-137 | 2′-F pyrimidines | Multiple myeloma | Downregulation of cell viability | (89) |
| EpCAM aptamer/ EpCAM receptor | siPLK1 | 2′-F pyrimidines | Breast cancer | Inhibition of tumor growth | (21) |
| A10 aptamer/PSMA | siPLK1 and siBCL-2 | 2′-F pyrimidines | Prostate cancer | Inhibition of tumor growth by A10-siPLK1 | (20,90) |
| CpG-ODN/SR, TLR9 | miR-146a | 2′-O-Methyl nucleotide | Del(5q) MDS and AML | Inhibition of NF-κB inflammatory activity and disseminated leukemia progression | (104) |
| CpG-ODN/ SR, TLR9 | siSTAT3 | Deoxyribonucleotides | Melanoma, multiple myeloma, and AML | Induction of antitumor immunity and Inhibition of tumor growth | (22,23,108) |
| CpG-ODN/ SR, TLR9 | siSTAT3 | Deoxyribonucleotides | MDSCs from Prostate cancer patients | Abrogation of MDSC immunosuppressive activity | (109) |
| ScFv/Her2 | siPLK1 | 2′-O-Methyl nucleotides | Breast cancer | Inhibition of tumor growth and metastasis and prolonged survival | (113) |
| mAb/Transferrin receptor | siLuciferase | Unmodified | Brain tumor | Significant reduction of luciferase expression | (115) |
| mAb (Hu3S193) /Lewis-Y | siSTAT3 | Unmodified | Lewis-Y+ A431 cells | Significant silencing of STAT3 | (116) |
| mAb/EGFR | siKRAS | Not reported | Colon Cancer | Significant inhibition of tumor growth | (117) |
| ScFv/PSMA | siNotch1 | Unmodified | Prostate cancer | Significant inhibition of tumor growth | (118) |
| mAb/PSMA | siTRIM24 | 2′-O-Methyl nucleotide | Prostate cancer | Significant inhibition of tumor growth | (119) |
| Dual variable domain antibody/ BCMA, SLAMF7 or CD138 | siCTNNB1 | 2′-O-Methyl, 2′-F nucleotides, PS bonds | Multiple myeloma | Significant downregulation of CTNNB1 | (120) |
| DARPin/EpCAM | siBCL-2 | 2′-O-Methyl nucleotides | Breast cancer | Sensitization to doxorubicin treatment | (123) |
| Centyrins/EGFR or EpCAM | siCTNNB1 | 2′-O-Methyl, 2′-deoxy-2′-F nucleotides,PS bonds | A431 tumor or colorectal cancer cell lines | Significant downregulation of CTNNB1 and reduction of colorectal cancer cell viability in vitro | (124) |
| Targeted extracellular vesicles (EVs) | |||||
| GE11 peptide/ EGFR | let-7a | Unmodified | Breast cancer | Inhibition of tumor growth | (140) |
| AS1411 aptamer/ nucleolin | let-7a | Not reported | Breast cancer | Inhibition of tumor growth | (141) |
| A15/integrin αvβ3 | miR-159 | Cholesterol-modified | Breast cancer | Inhibition of tumor growth | (142) |
| IL3/IL3-R | siBCR-ABL | Not reported | Chronic myeloid leukemia | Inhibition of tumor growth | (145) |
| Folate/FR | siSurvivin | 2′-F nucleotides | Colorectal cancer (PDX-CRC) | Inhibition of tumor growth | (147) |
| EGFR aptamer/EGFR | siSurvivin | 2′-F nucleotides | Breast cancer | Inhibition of tumor growth | (147) |
| PSMA aptamer (A9g)/PSMA | siSurvivin | 2′-F nucleotides | Prostate cancer | Inhibition of tumor growth | (147) |
FR: folate receptor; PSMA: prostate specific membrane antigen; dsRBD: double stranded RNA binding domain; DUPA: (2- [3-(1,3-dicarboxy propyl) ureido] pentanedioic acid); BCMA: B cell maturation antigen; ODN: oligodeoxynucleotides; SR: scavenger receptor; TLR: Toll-like receptor; A15: disintegrin and metalloproteinase 15; IL3: interleukin 3; IL3-R: interleukin 3-receptor; EGFR: epidermal growth factor receptor; ScFv: single-chain fragmented antibody; mAb: Monoclonal antibody; Si: siRNA (short interfering RNA); miR: microRNA; Bcl-2: B-cell lymphoma 2; Plk1: polo-like kinase 1; STAT3: signal transducer and activator of transcription 3; TRIM24: Tripartite motif-containing protein 24; 2′-F: 2′- fluoro; PS: phosphorothioate; HSPCs: hematopoietic stem/progenitor cells; Del(5q) MDS: chromosome-5q deletion myelodysplastic syndrome; AML: acute myeloid leukemia; MDSCs: myeloid derived suppressor cells; NF-κB: nuclear factor-κB; PDX-CRC: patient-derived colorectal cancer xenograft; Asterisk *, siRNA with internal folic acid modification.