Table 1.

A summary of Hurdles and Related Biomarkers.

Hurdle	Biomarker	References
Bloodstream	Complement Activation	[27,28,29,30,31,32,33,34]
	Anti-polymer Antibodies	[40,41,42,43,44,45]
	Protein Corona/Opsonization	[49,50,51,52,53]
Tumor Targeting	Passive Targeting Parameters	[81,82,83,84,85,86,87]
	Active Targeting Parameters	[80,104,105]
	Tumor Microenvironmental Factors	[113,115,120]
	Tumor Uptake	[122,123,128]
Intracellular Release	Enzyme Levels	[134,141,142]
	pH	[26,153,156,157]
	Redox Status	[154,155,159,160,161]
Additional Hurdles	Gene Mutations	[130]
	Cell Metabolites	[158,175]
	Age	[55,56,166]
	Sex	[55,56]
	Prior PT Treatments	[166]
	Health/Comorbidities	[12,54]
	Healthy Tissue Toxicity	[167]
	Exosomes	[189]