Table 3.

Summary of approaches to engineered fibrinolytic macromolecules and particles

Method	Advantages	Disadvantages
Macromolecules
Polymer coatings	Increased half-life	Reduced activity
	FDA approved materials available	Low specificity
		Low mobility in occluded vessels
Dendrimers	Increased half-life	Low specificity
	Reduced adsorption	Low mobility in occluded vessels
	Variable loading
Modified blood cells and cell mimics
Targeting	Targets components of thrombi	Low mobility in occluded vessels
	Reduced bleeding risk
Prophylaxis	Preventive Triggered release	Requires presence in blood before vessel occlusion
	Degrades clot from inside out	Complicated preparation/synthesis
Shear-activated release	Reduced bleeding risk	No shear in fully occluded vessel
	Triggered release	Requires presence in blood before vessel occlusion
Liposomes and polymer particles
PA Encapsulation	Increased half-life	Low specificity
	Controlled release	Difficult to control stability
	Reduces adsorption to fibrin	Low mobility in occluded vessels
PA Immobilization	Increased half-life	Reduced activity
	Decreased PA inhibition	Low mobility in occluded vessels
	Increased clot penetration
	Used in other clinical applications
Actuation
Sonic actuation	Enhanced lysis	Limited mobility in occluded vessels
	Locally induced flows	Limited targeting/specificity
	Successful phase II clinical trials
Magnetic actuation	Compatible with most engineered particles	Early stages of development (preclinical)
	High mobility, targeting	Challenging scale-up
	Local hyperthermia
	High local concentration