|About this Abstract
||MS&T23: Materials Science & Technology
||Society for Biomaterials: Student Poster Contest + Rapid Fire
||C-26: Nanoparticle-based drug delivery for the degradation of recalcitrant blood clots
||Hanyang Wang, Dante Disharoon, Shruti Raghunathan, Yolanda Fortenberry, Anirban Sen Gupta
|On-Site Speaker (Planned)
Arterial thrombosis, a leading cause of mortality, is characterized by pathological clots that restrict blood flow. Clots can be cleared using tissue plasminogen activator (tPA), but nearly half of arterial thrombi are recalcitrant to tPA degradation because they are stabilized by neutrophil extracellular traps (NETs), extrusions of DNA that reinforce clots structurally. Supplementing systemic tPA with deoxyribonuclease I (DNAse), which degrades NETs, has been shown to improve thrombolytic outcomes, but systemic tPA can cause iatrogenic hemorrhage. To mitigate this risk while maintaining thrombolytic potency, we developed clot-targeting tPA-loaded liposomal nanoparticles (tPA-LNP) that can be administered in a DNAse-rich solution. A thrombin-cleavable peptide was incorporated into tPA-LNP membranes such that thrombin, an enzyme upregulated in thrombosis, triggered release of the tPA payload. Additionally, tPA-LNP were decorated with a fibrin-binding peptide to localize their effects to a thrombus. tPA-LNP delivered in a DNAse-rich solution enhanced the lysis of tPA-recalcitrant clots in vitro.