Table 1.

Summary of TME modulation strategies for improving tumor nanomedicine delivery.

Modulation approach	Working mechanism	Agents	Tumor model	Reference
Improving interstitial transport	Reprogramming or depletion of TAF	Quercetin NP downregulating the expression of Wnt16	Bladder tumor	Hu et al. (2017)
		Losartan	Human pancreatic, skin and breast tumors	Diop-Frimpong et al. (2011); Chauhan et al. (2013)
		VDR ligand	Pancreatic cancer	Sherman et al. (2014)
		ATAR	Pancreatic cancer	Chronopoulos et al. (2016)
	ECM degradation	PEGPH20 (PEGylated hyaluronidase)	Pancreatic cancer	Hingorani et al. (2016)
		Matrix metalloproteinases-1 and − 8	Sarcoma	Mok et al. (2007)
		rtPA	Melanoma and Lung cancer	Kirtane et al. (2017)
	ECM reduction through inhibiting TAF activity	Cyclopamine	Pancreatic cancer	Jiang et al. (2017)
		IPI-926	Pancreatic cancer	Olive et al. (2009)
Advancing tumor perfusion	Tumor vessel dilation	BQ123	Colorectal carcinoma	Wang et al. (2017)
		Captopril	Glioma	Zhang et al. (2017b)
	Tumor vessel normalization	Chloroquine (Notch 1 signaling inhibition)	Melanoma	Maes et al. (2014)
		Imatinib mesylate	Lung cancer	Zhang et al. (2016)
		DC101	Colon adenocarcinoma, small cell lung carcinoma, glioblastoma multiforme, Mammary carcinoma,	Tong et al. (2004)
		Rapamycin	Melanoma	Guo et al. (2014)
		Dopamine	Colon and prostate tumor	Chakroborty et al. (2011)
Improving nanomedicine extravasation	Platelet depletion	R300 (Antiplatelet antibody)	Breast cancer	Li et al. (2017)
	Inflammatory mediators for enhancing vessel permeability	VEGF	Colon and Glioma carcinoma	Monsky et al. (1999)
		TNF- alpha	Melanoma and lymphoma	Curnis et al. (2002)
		Prostaglandin	Hepatocellular carcinoma	Tanaka et al. (2003)
	Pericyte depletion by inhibiting TGF signal pathway	TGF- type I receptor (TR-I) inhibitor	Gastric cancer, Pancreatic cancer.	Kano et al. (2007)
		A small-molecule TGF-β inhibitor, LY364947	Pancreatic cancer	Meng et al. (2013)
		ID11 (anti-TGF-β mAb)	Breast cancer	Liu et al. (2012)