Table 3.
The application of exosomes-based siRNA delivery system in cancer treatment in the last decade
| Exosome | The source of exosome | Therapeutic cargo | Loading method | Target gene | Mechanisms | Cancer types (cell lines) | Effects | References |
|---|---|---|---|---|---|---|---|---|
| Engineering exosome (tLyp-1-modified exosome) | HEK293T cells | siR1, siR2, siR3 | Electroporation | SOX2 | Knock-down the target gene expression | Non-small cell lung cancer (A549) | Reducing the stemness of cancer stem cells | [151] |
| Cancer-cell-derived exosome | Autologous breast cancer cells | siS100A4 | Incubation and extrusion method | S100A4 | Down-regulate the expression of S100A4 | Triple-negative breast cancer (4T1) | Inhibiting the growth of malignant breast cancer cells | [152] |
| HEK293T cells | si–c-Met | Lipofectamine 2000 transfection reagent | c-Met | Inhibiting the expression of c-Met | Gastric cancer (SGC7901) | Reversing the drug resistance of gastric cancer cells in vitro, and significantly inhibiting the tumor growth | [146] | |
| Engineering exosome (FA-displaying exosome) | HEK293T cells | Survivin siRNA | ExoFect exosomes transfection reagent | survivin | Knockdown the expression of survivin | Human oral epidermal carcinoma (KB) | Inhibiting tumor growth | [139] |
| Stem-cell-derived exosome | HEK293 cells, mesenchymal stem cell | PLK-1 siRNA | Electroporation | PLK-1 | Knockdown of PLK-1 mRNA and protein | Bladder cancer (UMUC3, SW780) | Inhibiting the bladder cancer cell proliferation | [142] |
| Engineering exosome (DARPin G3- modified exosome) | HEK293T cells | TPD52 siRNA | Electroporation | TPD52 | Binding specifically to HER2/Neu and siRNA molecules against TPD52 gene | Breast cancer (MDA-MB-231) | Inhibiting tumor growth | [153] |
| Normal fibroblast-like mesenchymal cells | KRAS siRNA | Electroporation | KRASG12D | Reducing KRASG12D mRNA levels and phosphorylated-ERK protein levels | Pancreatic cancer (MIA-PaCa-2, Capan-1) | Inhibiting tumor metastasis and increasing overall mouse survival | [154] | |
| HEK293T cells | HGF siRNA | Lipofectamine 2000 transfection reagent | HGF | Activating the HGF/c–Met signaling pathway | Gastric cancer (SGC‐7901) | Suppressing tumor growth and angiogenesis | [155] | |
| Cancer-cell-derived exosome | Cancer-associated fibroblasts | LINC00355 siRNA | Lipofectamine 2000 transfection reagent | LINC00355 | Decreasing the expression of LINC00355 | Bladder cancer (T24, 5367) | Repressing cell proliferation and invasion | [156] |
| Cancer-cell-derived exosome | Breast cancer | MALAT1 siRNA | Lipofectamine 2000 transfection reagent | MALAT1 | Down-regulating the expression of MALAT1 | Breast cancer (MCF-7, MDA-MB-231, MDA-MB-435S) | Suppressing cell proliferation | [157] |
| Cancer-cell-derived exosome | PANC-1 cells | PAK4 siRNA | Electroporation | PAK4 | Down-regulating the expression of PAK4 | Pancreatic cancer (PANC-1) | Inhibiting tumor growth and increasing mice survival | [158] |
| Human skin-derived fibroblasts(NB1RGB cells) | LCP1 siRNA | Electroporation | LCP1 | Suppressing LCP1 expression | Oral cancer (HSC-2, HSC-3, HSC-3-M3, HSC-4, Sa3, Ca9-22, KOSC-2, SAS, Ho-1-u-1, Ho-1-N-1, SAS-H1) | Suppressing the oncogenic activity of cancer cells | [159] | |
| HEK293T cells | TRPP2 siRNA | Incubation | TRPP2 | Suppressing TRPP2 protein expression levels | Human pharyngeal squamous cell carcinoma (FaDu) | Inhibiting migration, invasion and the EMT of cancer cells | [160] | |
| Cancer-cell-derived exosome | MCF-7, MCF-7/ADR cells | CD44 siRNA | Electroporation | CD44 | Suppressing CD44 expression | Breast cancer (MCF-7/ADR) | Reducing cell proliferation and enhancing susceptibility to DOX | [161] |
| MCF10A cells | CDK4 siRNA | Electroporation | CDK4 | Downregulating the CDK4 mRNA and protein expression | Breast cancer (MCF-7) | Inhibiting tumor growth | [162] | |
| HeLa cells | RAD51 siRNA, RAD52 siRNA | Electroporation | RAD51, RAD52 | Downregulating RAD51/RAD52 expression | Human cervical carcinoma (HT1080) | Resulting in apoptosis of the tumor cells | [40] | |
| Engineering exosome (iRGD peptide-modified exosome) | HEK293T cells | KRAS siRNA | Lipofectamine 2000 transfection reagent | KRAS | Silencing KRAS gene expression | Lung cancer (A549) | Inhibiting tumor growth | [163] |
| Stem-cell-derived exosome | Bone-marrow-derived mesenchymal stem cells | GRP78 siRNA | Lipofectamine 2000 transfection reagent | GRP78 | Inhibiting the expression of GRP78 | Hepatocellular carcinoma (HepG2, PLC) | Inhibiting the growth and invasion of the cancer cells | [145] |
| Stem-cell-derived exosome | Bone marrow mesenchymal stem cell | Galectin-9 siRNA | Electroporation | galectin-9 | tumor-suppressive macrophage polarization, cytotoxic T lymphocytes recruitment and Tregs downregulation | Pancreatic ductal adenocarcinoma (PANC-02) | Eliciting anti-tumor immunity | [100] |
| Engineering exosome (cRGD peptide-modified exosome) | RAW 264.7 cells | FGL1 siRNA, TGF-β1 siRNA | Exo-fect Exosome Transfection Reagent | FGL1, TGF-β1 | Blocking immune checkpoint FGL1 | Colorectal cancer(MC38) | An increased number of tumor infiltration CD8 + T cells, a decreased number of immunosuppressive cells, a significant anti-tumor effect | [150] |
| HEK293 cells | SCD-1 siRNA | Electroporation | SCD-1 | Regulating of fatty acids metabolism and increasing ROS level | Anaplastic thyroid carcinoma (Hth-7) | Inhibiting cellular proliferation and promoting cellular apoptosis | [164] | |
| Engineering exosome (iRGD peptide-modified exosome) | HEK-293 T cells | CPT1A siRNA | Lipofectamine 2000 transfection reagent | CPT1A | Regulating fatty acid oxidation | Colon cancer (HCT116, sw480) | Reversing oxaliplatin resistance and inhibiting tumor growth | [147] |
| Natural killer cells NK92MI | BCL-2 siRNA | Co-incubation | BCL-2 | Inhibiting the expression of BCL2 | Breast cancer (MCF-7, SKBR3, T-47D, MDA-MB-231) | Enhancing cancer cell’ intrinsic apoptosis | [141] | |
| Engineering exosome (E3 aptamer- modified exosome) | HEK293T cells | SIRT6 siRNA | Electroporation | SIRT6 | Inhibiting the expression of SIRT6 | Prostate cancer (C42B, DU145) | Inhibiting tumor growth and metastasis | [165] |
| Engineering exosome (EGFR RNA aptamer-modified exosome) | HEK293T cells | Survivin siRNA | ExoFect exosome transfection | survivin | Knockdown the expression of survivin | Non-small-cell lung cancer (A549) | Leading to potent gene knockdown, chemotherapy sensitization, and tumor regression | [166] |
| Engineering exosome (RNA nanotechnology- modified exosome) | HEK293T cells | Survivin siRNA | survivin | Knockdown the expression of survivin | Prostate cancer breast cancer colorectal cancer | Inhibiting tumor regression | [143] |