Epithelial-mesenchymal transition (EMT) has emerged as a key regulator of cell invasion and metastasis in cancers. However, although EMT represents a relevant therapeutic target for cancer treatment, its application in the clinic is still limited due to various reasons, including appropriate drug delivery. Different nanomaterials may be used to counteract EMT induction, providing novel therapeutic tools against many different cancers. We discuss the application of various nanomaterials for EMT-based therapies in cancer, the therapeutic relevance of some of the proposed EMT targets, and the potential benefits and weaknesses of each approach.
Entry | NPs | Combined Treatments | Target Cells | Cancer Tissues | Regulation of EMT Markers | Biological Effects | Refs |
---|---|---|---|---|---|---|---|
1 | Gold nanoparticles | none | A2780, OVCAR5 SKOV3-ip |
Epithelial ovarian cancer | E-cadherin↑ N-cadherin↓ Snail↓ p42/44↓ MAPK↓ |
Inhibition of cell proliferation; Reversion of epithelial plasticity; Inhibition of EMT |
[48] |
2 | Gold nanoparticles | none | A2780, OVCAR5 and SKOV3-ip |
Epithelial ovarian cancer | ALDH1↓, CD44↓, CD133↓, Sox2↓, MDR1↓, ABCG2↓ Akt signaling↓ NF-κB signaling↓ E-Cadherin↑ β-Catenin↑ Vimentin↓ α-SMA↓ |
Sensitivity to cisplatin; Suppression cancer stem cell proprieties; Inhibition of EMT |
[49] |
3 | Gold nanoparticles | none | PANC-1, AsPC-1 and HPAF II | Pancreatic cancer | E-cadherin↑ N-cadherin↓ Vimentin↓ |
Sensitivity to gemcitabine; Suppression cancer stem cell proprieties; Inhibition of EMT |
[50] |
4 | Gold nanoparticles | none | HUVECs B16F10 |
Melanoma Blood vessels |
E-Cadherin↑ ZO-1↑ Vimentin↓ C-myc↓ MMP2↓ |
Inhibition of cell migration; Inhibition of EMT |
[51] |
5 | Gold nanorods | none | HeLA MCF-7 |
Cervical cancer Breast cancer |
Vimentin↓ N-cadherin↓ |
Inhibition of collective migration; Decrease of EMT markers | [52] |
6 | Gold Nanoparticles | Cold plasma | T98G A459 |
Glioblastoma Lung cancer |
E-Cadherin↑ N-Cadherin↓ Slug↓ ZEB1↓ PI3K/AKT patwhay ↓ |
Apoptosis; Reduction of cell proliferation; Inhibition of EMT; Decrease in sphere formation; Decrease in self-renewal capacity |
[53] |
7 | Titanium dioxide | none | A459 | Epithelial lung cancer | Smad2/3↓ E-Cadherin↑ N-cadherin↓ |
Inhibition of TGF-β-Mediated Cell Migration; Suppression of TGF-β-Induced EMT; Attenuation of TGF-β Signaling |
[54] |
8 | Titanium dioxide Silicon dioxide |
none | LX-2 | Fibrosis | N-Cadherin↓ E-Cadherin↑ |
Inhibition of EMT; Inhibition of fibrosis; Reduction of adhesion and migration profiles |
[55] |
9 | ZnO Nanostructures | none | T98G SNU-80 H-460 |
Glioblastoma Thyroid cancer Lung cancer |
N-Cadherin↓ ZEB1↓ |
Cell death; Apoptosis; Reduction of cell invasion; Inhibition of EMT |
[56] |
10 | D, L-lactic-co-glycolic acid (PLGA) | α–Mangostin | PANC-1, AsPC-1, MIA PaCa-2; Human CSCs, KrasG12D mouse CSCs |
Pancreatic cancer | E-cadherin↑ N-cadherin↓ Slug, Snail1, ZEB1↓ Nanog, c-Myc, Oct4↓ Shh pathway↓ Gli targets↓ |
Inhibition of cancer growth; development; metastasis; inhibition of pluripotency; Inhibition of EMT |
[57] |
11 | D, L-lactic-co-glycolic acid (PLGA) | Anthothecol | PANC-1, AsPC-1, MIA PaCa-2; Human CSCs, KrasG12D mouse CSCs |
Pancreatic cancer | E-cadherin↑ N-cadherin↓ Slug, Snail, ZEB1↓ Nanog, c-Myc, Oct4↓ Shh pathway↓ Gli targets↓ |
Inhibition of cell proliferation; invasion; migration; induction of apoptosis; inhibition of pluripotency; Inhibition of EMT |
[58] |
12 | D, L-lactic-co-glycolic acid (PLGA | Wedelolactone | MDA-MB-231 Breast cancer stem cells |
Triple negative breast cancer | E-Cadherin↑ N-Cadherin↓ TWIST1↓ Snail↓ Vimentin↓ |
Retarded migration and invasion; Reduction of cell viability; Apoptosis; Inhibition of EMT; Reduction of pluripotency; Drug sensitivity to paclitaxel |
[59] |
13 | D, L-lactic-co-glycolic acid (PLGA) | Salinomycin | AsPC-1 | Pancreatic cancer | E-Cadherin↑ β catenin↑ TGFβ R-1↓ TGFβ R-2↓ |
Inhibition of EMT; Apoptosis |
[60] |
14 | Polymeric micelles | Salinomycin | A459 | Lung cancer | Vimentin↓ | Inhbition of EMT; Reversion to epithelial phenotype; Reduction of cell migration; Prevention of P-gp efflux |
[61] |
15 | Silver nanoparticles | Gallic Acid | A459 | Lung cancer | Vimentin↓ N-cadherin↓ Snail1↓ E-cadherin↑ |
Loss of radiation-induced metastasis; Inhibition of EMT |
[62] |
16 | Curcumin loaded selenium nanoparticles (Se-Cu NPs) | Curcumin | HCT116 | Colon cancer | CD44↓ N-Cadherin↓ |
Induction of autophagy; Induction of apoptosis; Induction of cell cycle arrest; Inhibition of EMT |
[63] |
17 | Curcumin loaded selenium nanoparticles (Se-Cu NPs); CD44-targeted DOX loaded nanoparticles (PSHA-DOXNPs) |
Curcumin, Doxorubicin |
HCT116 | Colon cancer | N-Cadherin↓ Vimentin↓ Snail1↓ CD44↓ MMP2↓ MMP4↓ |
Induction ROS levels; Decreased mitochondrial membrane potential; Induction cell cycle arrest; Apoptosis; Inhibition of EMT |
[64] |
18 | Gold Nanoparticles | Quercetin | MCF-7 MDA-MB-231 HUVECs |
Breast cancer | E-Cadherin↑ N-Cadherin↓ Vimentin↓ Snail↓ Slug↓ TWIST1↓ MMP2/9↓ EGFR/VEGFR-2 signalling↓ |
Inhibition of EMT; Inhibition of angiogenesis; Inhibition of cell invasion |
[65] |
19 | Liposomal | Quercetin | Eca109/9706 | Esophageal squamous cell carcinoma |
E-Cadherin↑ | Apoptosis; Inhibition of EMT |
[66] |
20 | Mesoporous silica; PEG-PLA micelles | Epigallocatechin gallate/iron | 4T1 | Mouse breast cancer | MMP2/9 ↓ VEGF↓ Vimentin↓ E-cadherin↑ |
Suppression of metastasis; Inhibition of EMT |
[67] |
21 | Layered double hydroxide | Etoposide | U87MG Glioblastoma stem cells (GSCs) |
Glioblastoma | Sox2↓ Oct4↓ Nanog↓ Nestin↓ Snail↓ N-Cadherin↓ E-Cadherin↑ PI3K/AKT/mTOR↓ WNT/GSK3β/β-catenin↑ |
Inhibition of cell proliferation; Down-regulation of GSCs stemness; Inhbition of EMT |
[68] |
22 | Liposomes | ADH-1 peptide Paclitaxel |
MCF7-paclitaxel resistant | Breast cancer | N-Cadherin↓ E-Cadherin↑ |
Improvement of chemosensitivity; Inhibition of cell migration; Inhibition of EMT |
[69] |
23 | Liposomes | ADH-1 peptide DOX Hyaluronic Acid |
A459 | Lung cancer | N-Cadherin↓ CD44↓ |
Drug sensitivity; Reduction of cell migration; Inhibition of EMT |
[70][71] |
24 | Gold nanoparticles | Dexamethasone (DSH) thiol derivative Withaferin (WFA) |
B16F10 | Murine melanoma | E-Cadherin↑ Vimentin↓ pAKT/AKT signalling↓ |
Induction of apoptosis; Inhibition of cell cycle; Induction of MET; Inhibition of EMT |
[72] |
25 | Zinc arsenite | Arsenic trioxide | Hep3b, HepG2, Bel7402 and MHCC97L | Liver cancer | E-Cadherin↑ Vimentin↓ Slug↓ SHP-1/JAK2/STAT3↓ |
Suppress tumor initiation and growth; Suppression metastasis Inhibition stemness and EMT |
[73] |
26 | Albumin based nanoparticles | Arsenic trioxide | in 5-8F CNE-2 |
Nasopharyngeal carcinoma | E-Cadherin↑ N-Cadherin↓ Vimentin↓ |
Inhibition of colony formation; Inhibition of cell invasion; Inhibition of EMT |
[74] |
27 | Liposome | 188Re | ES-2-luc | Ovarian cancer | E-Cadherin↑ Vimentin↓ p53↑ |
Switch to mitochondrial phosphorylation; Reactivation of p53 function; Inhibition of EMT |
[75] |
28 | Liposome | 188Re | FaDu | Head and neck squamous cell carcinoma | Let-7↑ | Suppression of tumor growth | [76] |
29 | Liposome | 188Re | FaDu, SAS |
Head and neck squamous cell carcinoma | E-Cadherin↑ N-Cadherin↓ TWIST1/2 ↓ Vimentin↓ ZEB1↓ Slugs↓ |
Inhibition of cell proliferation; Cell death; Inhibition of EMT |
[77] |
30 | Liposome | Simvastatin, Paxicitel | A549T PC9 TAM (tumor associated macrophages) |
Lung and prostate cancer | FAK↓ ERK/AKT↓ TNF-α↑ TGFβ↓ LXR/ABCA1↓ E-Cadherin↑ Vimentin↓ |
Inhibition of EMT; Sensitization to paxicitel; Repolarization of TAM; Regulation of cholesterol metabolism |
[78] |
31 | Carboxymethyl dextran (CMD)-chitosan nanoparticles (ChNPs) | Snail siRNA DOX |
HCT-116 | Colon cancer | MMP9 ↓ Vimentin↓ E-cadherin↑ |
Inhibition cell growth; apoptosis; inhibition of migration; Inhibition of EMT |
[79] |
32 | Carboxymethyl dextran (CMD)-chitosan nanoparticles (ChNPs) | Snail siRNA SN38 |
PC-3 | Prostate cancer | E-cadherin↑ Claudin-1↑ |
Reduction of cell proliferation; Reduction of cell migration; Inhibition of EMT |
[80] |
33 | Carboxymethyl dextran (CMD)-chitosan nanoparticles (ChNPs) | Snail siRNA HMGA2 siRNA DOX |
A459 | Lung cancer | HMGA2↓ E-cadherin↑ Vimentin↓ MMP9↓ |
Apoptosis; Reduction in cell migration; Drug sensitivity; Inhibition of EMT |
[81] |
34 | Polypeptide micelles (PEG–PLL–PLLeu) | ZEB1 siRNA DOX |
H460 | Non-small cell lung cancer (NSCLC) | ZEB1↓ E-cadherin↑ SOX2↓ ABCG2↓ |
Inhibition of EMT; Repression of CSC properties; Reduction of cell invasion; Sensitivity to DOX |
[82] |
35 | Polyamidoamine dendrimers (PAMAM) and Hyaluronic-acid conjugated mesoporous silica nanoparticles (MSN-Has) | TWIST1 siRNA Cisplatin |
F2 Ovcar8 |
Ovarian cancer | Vimentin↓ E-Cadherin↑ N-Cadherin↓ |
Chemosensitivity to cisplatin; Inhibition of EMT |
[83][84] |
36 | Mesoporous Silica | TWIST1 siRNA | MDA-MB-435S | Melanoma | Vimentin↓ CCL2↓ |
Inhibition of migration; Inhibition of EMT |
[85] |
37 | Chitosan-coated nanoparticles | TWIST1 siRNA | CNE2 | Nasopharyngeal carcinoma | p-ERK↑ | Sensitivity to radiation; Irradiation-induced apoptosis |
[86] |
38 | Polyamidoamine dendrimers (PAMAM) | TWIST1 siRNA | SUM1315 | Triple negative breast cancer | N-Cadherin↓ Vimentin↓ |
Reduction of cell migration and invasion; Inhibition of EMT |
[87] |
39 | (PLGA)2-PEI-DMMA nanoparticles | NgBR siRNA | HUVECs MDA-MB-231 4T1 |
Breast cancer | Vimentin↓ E-Cadherin↑ |
Inhibition of endothelial cell migration; Suppression of cancer cell invasion Normalization of tumor blood vessel; Inhibition of EMT |
[88] |
40 | ECO lipid carrier | β3 integrin siRNA | MDA-MB-231 | Triple negative breast cancer | PAI-1↓ N-cadherin↓ E-cadherin↑ CK19↑ |
Inhibition of TGFβ-mediated cytostasis; Inhibition of TGFβ-mediated EMT; Inhibition of TGFβ-mediated invasion; Inhibition of 3-dimensional organoid growth; Inhibition of EMT |
[89] |
41 | ECO lipid carrier | DANCR siRNA | MDA-MB-231 BT549 |
Triple negative breast cancer | β-catenin↓ ZEB1↓ Stat proteins↓ N-cadherin↓ Survivin↓ WNT signaling↓ |
Inhibition of cell invasion; Inhibition of cell migration; Reduction of survival; Reduction in tumor spheroid Formation; Inhibition of cell proliferation Inhibition of EMT |
[90] |
42 | Poly(lactide-co-glycolide) acid nanoparticles (PLGA NPs) | DCAMKL-1 siRNA | HCT116 | Colon cancer | miRNA 200a↑ miRNA let-7a↑ E-Cadherin↑ ZEB1/2↓ Snail↓ Slug↓ |
Inhibition of tumor growth; Inhibition of EMT |
[91] |
43 | Polyethylene glycol-polyethyleneimine-chlorin e6 | Wnt-1 siRNA | KB | Oral squamous cell carcinoma | Wnt-1 ↓ β-catenin↓ Vimentin↓ |
Inhibition of cell growth; sensibility to PDT; Inhibition of EMT |
[92] |
44 | Cationic solid lipid nanoparticles (SLN) | STAT3 decoy oligodeoxynucleotide | A2780 SKOV3 |
Ovarian cancer | E-Cadherin↑ Snail↓ MMP9↓ |
Induction of cell death; Apoptotic and autophagy cell death; Inhibition of invasion; Inhibition of EMT |
[93] |
45 | Gelatin nanoparticles | AXL siRNA | H820 and H1975 erlotinib-resistant | Non-small cell lung cancer | MMP9↓ MMP2↓ Vimentin↓ N-cadherin↓ |
Overcome of chemoresistance to tyrosine kinase inhitors; Inhbition of EMT |
[94] |
46 | Polyethylene glycol–polyethylenimine–magnetic iron oxide (PEG-PEI-IONPs) | microRNA-21 antisense oligonucleotides; Gemcitabine |
PANC-1 MIA PACA-2 |
Pancreatic cancer | PTEN↑ PDCD4↑ Vimentin↓ E-Cadherin↑ |
Inhibition of cell proliferation; Apoptosis; Inhibition of invasion and cell migration; Inhibition of EMT |
[95] |
47 | Lipid–polymer hybrid nanoparticles modified with CPP | Afatinib; miR-139 |
Caco-2 | Colorectal cancer | E-Cadherin↑ β-catenin↓ Slug↓ |
Inhbition of EMT; Sensitivity to afatinib; Reduced cancer cell migration |
[96] |
48 | Gelatinases-stimuli poly(ethylene glycol)-peptide-poly(ε-caprolactone) copolymer | miR-200c Docetaxel |
BGC-823 CSCs and non-CSCs |
Gastric adenocarcinoma | E-Cadherin↑ CD44↓ |
Drug sensitivity to DOC; Inhibition of EMT |
[97] |
Entry | NPs | Compound/Drugs Carried | Animal Models | Diseases Model | Biological Effects | Refs |
---|---|---|---|---|---|---|
1 | Gold | none | orthotopic ovarian tumor models (A2780 cells or SKOV3-ip) | Ovarian cancer | Inhibition of tumor growth; Inhibition of metastasis; Inhibition of EMT |
[48] |
2 | Gold | none | Female athymic nude mice orthotopic ovarian tumor models (SKOV3-ip) | Ovarian cancer | Drug sensitivity to cisplatin; Reduction of tumor growth; Inhibition of EMT |
[49] |
3 | Gold | none | Female C57BL6 mice | Melanoma | Improvement of vascular morphology; Increase vascular perfusion and decrease permeability; Alleviation of hypoxia; Reduction of lung metastasis; Inhibition of EMT |
[51] |
4 | Gold Nanoparticles | Cold plasma | Athymic balb/c female nude mice U87MG xenograft model |
Glioblastoma Lung cancer |
Reduction tumor growth | [53] |
5 | Titanium dioxide | none | Wild-type zebrafish AB strain; Male C57BL/6 mice |
Caudal regeneration; Colitis |
Impairment of Caudal Fin Regeneration; Colon injury |
[54] |
6 | D, L-lactic-co-glycolic acid (PLGA) | α–Mangostin | KC (PdxCre;LSL-KrasG12D); KPC (PdxCre;LSLKrasG12D;LSL-Trp53R172H |
Pancreatic cancer | Inhibition of cancer growth; development; metastasis; Inhibition of EMT |
[57] |
7 | D, L-lactic-co-glycolic acid (PLGA) | Wedelolactone | Female Swiss Albino mice | Triple negative breast cancer | Reduction tumor volume; Reduction cancer stem cells |
[59] |
8 | D, L-lactic-co-glycolic acid (PLGA) | Salinomycin | Female athymic nude mice AsPC-1-luc orthotopic model |
Pancreatic cancer | Reduction tumor growth; Inhibition of EMT |
[60] |
9 | Curcumin loaded selenium nanoparticles (Se-Cu NPs) | Curcumin | Ehrlich’s ascites carcinoma (EAC)-bearing mice. |
Colon cancer | Reduction tumor mass; Increasing mean survival time |
[63] |
10 | Curcumin loaded selenium nanoparticles (Se-Cu NPs); CD44-targeted DOX loaded nanoparticles (PSHA-DOXNPs) |
Curcumin, Doxorubicin |
Ehrlich’s ascites carcinoma (EAC)-bearing mice. |
Colon cancer | Decreased tumor burden; Increased survival |
[64] |
11 | Gold Nanoparticles | Quercetin | Female Sprague-Dawley rats | Breast cancer | Inhibition of tumor growth; Inhibition of metastasis |
[65] |
12 | Mesoporous silica; PEG-PLA micelles | Epigallocatechin gallate/iron | Female balb/c mice |
Breast cancer | Suppression of metastasis; Inhibition of EMT |
[67] |
13 | Layered double hydroxide | Etoposide | Female BALB/c nude mice | Glioblastoma | Reduction of tumor growth; Induction of apoptosis; Inhibition of pluripotency; Inhibition of EMT |
[68] |
14 | ADH-1 peptide-modified liposomes | Paclitaxel | Female BALB/c nude mice | Breast cancer | Inhibition of tumor growth; Enhancement of chemosensitivity |
[69] |
15 | Gold nanoparticles | Dexamethasone (DSH) thiol derivative Withaferin (WFA) |
Old female C57BL/6J mice | Melanoma | Induction of apoptosis; Inhibition of tumor growth; Reduction in mice mortality; Inhibition of EMT |
[72] |
16 | Albumin based nanoparticles | Arsenic trioxide | Xenograft model | Nasopharyngeal carcinoma | Reduction tumor growth; Inhibition of EMT |
[74] |
17 | Liposome | 188Re | Balb/C nude mice Orthotopic xenograft model | Ovarian cancer | Reactivation p53; Switch to oxidative phosphorylation; Inhibition of EMT |
[75] |
18 | Liposome | 188Re | Balb/C nude mice Orthotopic xenograft model | Head and neck squamous cell carcinoma | Suppression of tumor growth | [76] |
19 | Liposome | 188Re | Balb/C nude mice Orthotopic xenograft model | Head and neck squamous cell carcinoma | Suppression of tumor growth; Survival; Inhibition of EMT; Inhibition of proliferation markers; Accumulation in tumor site |
[77] |
20 | Liposome | Simvastatin, Paxicitel | A549T xenograft mouse model | Lung cancer | Reversion of chemoresistance to PTX in vivo; Arrest of cell growth; Inhibition of EMT; Change of cell polarization of TAM in vivo |
[78] |
21 | Polypeptide micelles (PEG–PLL–PLLeu) | ZEB1 siRNA DOX |
Female BALB/c nude mice H460 xenograft model |
Non-small cell lung cancer (NSCLC) | Inhibition of EMT; Repression of CSC properties; Inhibition of metastasis; Inhibition of tumor growth |
[82] |
22 | Polyamidoamine dendrimers (PAMAM) and Hyaluronic-acid conjugated mesoporous silica nanoparticles (MSN-Has) | TWIST1 siRNA Cisplatin |
NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice | Ovarian cancer | Inhibition of tumor growth; Sensitivity to cisplatin; Inhibition of EMT |
[83][84] |
23 | Mesoporous Silica | TWIST1 siRNA | NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) | Melanoma | Reduction of tumor burder; Inhibition of EMT |
[85] |
24 | PEI-PDHA PEG-PDHA P85-PEI/TPGS |
TWIST1 siRNA Snail siRNA Paclitaxel |
4T1 tumor-bearing mice models | Breast cancer | Reduction of metastasis; Inhibition of cell invasion; Inhibition of ECM degradation Inhibition of tumor growth |
[111][112] |
25 | Polyamidoamine dendrimers (PAMAM) | TWIST1 siRNA | NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice | Breast cancer | Biodistribution in tumor site | [87] |
26 | (PLGA)2-PEI-DMMA nanoparticles | NgBR siRNA | Female BALB/c nude mice Orthotopic model |
Breast cancer | Reduction of metastasis | [88] |
27 | ECO lipid carrier | β3 integrin | Female nude mice (nu/nu Balb/c background) | Triple negative breast cancer | Reduction of primary tumor burden; Inhibition of metastasis; Inhibition of EMT |
[89] |
28 | ECO lipid carrier | DANCR siRNA | Nude athymic mice MDA-MB-231 and BT549 xenograft model |
Triple negative breast cancer | Reduction of tumor growth; Inhibition of EMT |
[90] |
29 | Poly(lactide-co-glycolide) acid nanoparticles (PLGA NPs) | DCAMKL-1 siRNA | Male athymic nude mice (NCr-nu/nu) HCT116 cells orthotopic models |
Colon cancer | Arrest in tumor growth; Inhibition of EMT; Regulation of oncogenic miRNAs network |
[91] |
30 | Polyethylene glycol–polyethylenimine–magnetic iron oxide (PEG-PEI-IONPs) | microRNA-21 antisense oligonucleotides; Gemcitabine |
Female BALB/c nude mice | Pancreatic cancer | Reduction tumor growth; Inhibition of metastasis |
[95] |
31 | Gelatinases-stimuli poly(ethylene glycol)-peptide-poly(ε-caprolactone) copolymer | miR-200c Docetaxel |
BGC-823 gastric tumor-bearing mice | Gastric adenocarcinoma | Suppression tumor growth; Drug sensitivity; Inhibition of EMT |
[97] |
This entry is adapted from the peer-reviewed paper 10.3390/cancers12010025