Abstract 14584: Successful Cardiac Targeting of a Superoxide Dismutase-Loaded Nanoparticle in a Rodent Ischemia-Reperfusion Model

Introduction: Encapsulating superoxide dismutase (SOD) in a semi-porous nanoparticle (NP) preserves myocardial function in rats following ischemia-reperfusion (I/R) injury. Cardiac targeting maximizes enzyme efficacy by enhancing retention. This study describes the formulation, characterization, and functional analysis of cardiac myosin (CM) targeted SOD NP. Method Targeted SOD NP with anti-CM antibody was developed in three steps and characterized with dynamic light scattering (DLS), colorimetric SOD assay, and in vitro imaging with isolated mature rat cardiomyocytes. In vivo function was assessed with a rat model of cardiac I/R injury in which the LAD was occluded for 60 minutes, ligation was released, and treatments were injected in the myocardium. Animals were recovered for 28 days and terminal pressure-volume (PV) loop analysis was performed. Result Anti-CM SOD NP was formulated by first encapsulating SOD in a polymersome containing an azide functional group. Second, a photoreactive antibody-binding domain was bonded to the azide. Third, covalent bonding of the NP to anti-CM antibody was performed with UV-light activation (Fig 1A). Consistent size was confirmed by DLS during formulation (Fig 1B). In vitro visualization of rhodamine-tagged anti-CM NP bound to mature cardiomyocytes confirmed antibody conjugation (Fig 1C). SOD activity was preserved during formulation and after degradation with Triton X, confirming conjugation did not affect porosity (Fig 1D). 53 rats underwent I/R injury and were randomized to 4 treatment groups of which 44 survived to terminal analysis (Fig 1E). Rats injected with anti-CM SOD NP had preserved EF (med 57%) and significant improvement in EF compared to PBS (med 40%, p=0.04). Conclusion Cardiac targeting of SOD NP with anti-CM antibody was successful and preserved EF in a rat I/R model. Ongoing future steps include correlation of scar volume with PV loop data, myocardial retention analysis and biodistribution of anti-CM NP.