Table 1.
Summary of tumor microenvironment modulation strategies for improving tumor nanomedicine delivery.
| Modulation strategies | Main working mechanism | Modulation agents | Tumors | References |
|---|---|---|---|---|
| Improving tumor perfusion | Tumor vessel normalization by blocking tumor proangiogenic signaling | DC101 (VEGF mAb) | Mammary carcinoma, small cell lung carcinoma, glioblastoma multiforme, colon adenocarcinoma | Tong et al., 2004 |
| Bevacizumab (VEGF mAb) | Colon carcinoma, melanoma | Ellis, 2005; Turley et al., 2012 | ||
| SST0001 (Heparanase inhibitor) | Myeloma | Ritchie et al., 2011 | ||
| Rapamycin (mTOR signaling inhibition) | Melanoma | Guo et al., 2014 | ||
| Chloroquine (Notch 1 signaling inhibition) | Melanoma | Maes et al., 2014 | ||
| Dopamine (D2 receptors-angiopoietin 1 activation) | Prostate and colon tumor | Chakroborty et al., 2011 | ||
| Imatinib mesylate (PDGF signaling inhibition) | Lung carcinoma | Zhang et al., 2016d | ||
| Tumor vessel dilation | BQ123 (ETA antagonist) | Colorectal carcinoma | Wang et al., 2017 | |
| Captopril (hypotensor) | Glioma | Zhang et al., 2017a | ||
| Facilitating nanomedicine extravasation | Inflammatory mediators for enhancing vessel permeability | TNF- alpha | lymphoma and melanoma | Curnis et al., 2002; Seki et al., 2011 |
| Prostaglandin I2 | Hepatocellular carcinoma | Tanaka et al., 2003 | ||
| VEGF | Glioma and colon carcinoma | Monsky et al., 1999 | ||
| Nitroglycerin (NG) | Sarcoma | Seki et al., 2009 | ||
| Pericyte depletion by inhibiting TGF signal pathway | A small-molecule TGF-β inhibitor, LY364947 | Pancreatic cancer | Meng et al., 2013 | |
| TGF- type I receptor (TR-I) inhibitor | Pancreatic cancer, gastric cancer | Kano et al., 2007 | ||
| ID11 (anti-TGF-β mAb) | Breast carcinoma | Liu et al., 2012 | ||
| Platelet depletion | Antiplatelet antibody R300 | Breast cancer | Li et al., 2017 | |
| Enhancing interstitial transport | Direct ECM degradation | Matrix metalloproteinases-1 and−8 | Sarcoma | Mok et al., 2007 |
| Hyaluronidase and hyaluronidase-loaded nanoparticles | Pancreatic cancer, breast cancer | Provenzano et al., 2012; Gong et al., 2016; Zhou et al., 2016 | ||
| PEGPH20 (PEGylated hyaluronidase) | Pancreatic cancer | Jacobetz et al., 2012; Hingorani et al., 2016 | ||
| rtPA | Lung cancer, melanoma | Zhang et al., 2016b; Kirtane et al., 2017 | ||
| ECM reduction by inhibiting TAF activity | IPI-926 (Hh inhibitor) | Pancreatic cancer | Olive et al., 2009 | |
| Cyclopamine (Hh inhibitor) | Pancreatic cancer | Zhang et al., 2016c; Jiang et al., 2017 | ||
| TAF depletion or reprogramming | Losartan | Human breast, pancreatic, and skin tumors | Diop-Frimpong et al., 2011; Chauhan et al., 2013 | |
| VDR ligand | Pancreatic cancer | Sherman et al., 2014 | ||
| ATAR | Pancreatic cancer | Froeling et al., 2011; Chronopoulos et al., 2016 | ||
| Quercetin nanoparticles downregulating Wnt16 expression | Bladder carcinoma | Hu et al., 2017 |