Proton-impact high-Z metallic nanoparticles produce burst emissions of low-energy electrons, including interatomic Coulomb decay electrons and Auger electrons (0-1000 eV), termed as the Coulomb nanoradiator (CNR) effect, thus damaging and having a therapeutic effect on the pathological tissues impacted by the nanoparticles. This pilot study attempts to investigate the macrophage-mediated uptake of iron-oxide nanoparticles (Fe$_3$O$_4$, FeO-NP) in the thrombus for potent CNR-based thrombolysis. In a ferric-chloride mouse arterial thrombus model, FeO-NP were intravenously injected, and the thrombus uptake of the iron NP was evaluated in the temporally-extracted vessels with Perl's Prussian blue staining. The NP distribution in the thrombus dependened on the post-injection circulation time, and no iron uptake was observed at either 30 minutes or 2 hours after injection. In contrast, homogeneous uptake of iron NP was observed in the central thrombus at 22 hours post-injection while no uptake was observed in the normal intima or adventia. These results suggest potent noninvasive CNR thrombolysis when using a high-energy traverse Bragg-peak proton or ion beam.

Keywords: Iron-oxide nanoparticles, Proton, Nanoradiator

proton-impact high-Z 금속나노입자는  원자간쿨롱붕괴-전자, Auger전자 등 다발성 저에너지전자방출의 (0-1000 eV) 쿨롱나노라디에타효과 (Coulomb nanoradiator effect; CNR)를 생성, 나노입자가 축적된 병소조직을 손상-치료효과를 유발한다. 본 pilot 연구는 혈전내 대식세포-중개 금속나노입자의 축적여부에 따른 CNR-혈전용해치료 가능성을 타진하기 위해, ferric-chloride 마우스 경동맥 혈전모델에서, Iron oxide 나노입자 (Fe$_3$O$_4$)를 정맥주사하고, 혈전내 나노입자의 축적 여부를 circulation time 함수로 적출된 혈관에서 Perl's Prussian blue 염색법으로 관찰하였다. 주사 후 경과시간에 따라 혈전내 축적양상은 달랐으며, 30분, 2시간 뒤에는 혈전내 축적이 관찰되지 않았으나 22시간 뒤, 혈관의 내막이나 adventia등에서는 나노입자의 축적이 일어나지 않는데 반해 혈전중심부위에서 철나노입자의 축적을 최초로 확인하였다. 동 결과는 Traversing Bragg-peak 양성자 또는 중이온 빔을 이용 쿨롱나노라디에타 효과에 의한 새로운 비침습적 혈전용해법 가능성을 제시하고자 한다.

Keywords: 철나노입자, 양성자, 나노라디에타