학술논문
과산화수소 감응 및 혈전 표적을 통한 폐색성 혈관 질환 진단치료 나노 입자 / H2O2-Activatable and Thrombus Targeting Nanoparticles as Theranostics for Obstructive Vascular Diseases
Document Type
Dissertation/ Thesis
Author
Source
Subject
Language
English
Abstract
혈전증은 심근경색 및 뇌졸중을 일으키며 생명을 위협하는 심각한 심혈관 질환이다. 과산화수소(H2O2)는 혈전의 주요 성분인 혈소판을 활성화시키고 혈관을 손상시키는 것으로 알려져 있어 혈전증의 바이오 마커로서 큰 가능성을 가지고 있다. 아스피린은 혈관질환의 치료 및 예방에 널리 사용되고 있으나 혈장 내 반감기가 짧고 혈전을 표적하여 혈소판을 활성화시키는H2O2 생성을 억제할 수는 없다. 본 연구에서는 혈전을 표적화 하여H2O2를 신속하게 제거한 후 살리실레이트를 방출할 수 있는Thrombus targeting poly(salicylate-co-oxalate) (TT-PSOX) 나노입자를 기반으로 하는 H2O2 활성 및 혈전표적 나노약물을 개발하였다. TT-PSOX 나노입자는 활성화된 혈소판에서 종양괴사인자 알파(TNF-α) 및 가용성 CD40 리간드(sCD40L) 의 발현을 억제하여 내 인성 항염증, 항혈소판 및 항산화 작용을 나타냈다. 경동맥 혈전증의 마우스 모델에서 TT-PSOX나노입자구는 폐색성 혈전을 특이적으로 표적으로 하여 형광신호를 현저히 향상시키고 혈전형성을 현저하게 억제했다. 그러므로, TT-PSOX 나노입자는 폐색성 혈전증과 같은 고농도의 H2O2와 관련된 각종 심혈관 질환의 진단 및 치료에 이용될 수 큰 잠재력을 지닌 것으로 판단된다.
Thrombosis is one of the major life-threatening diseases worldwide, causing myocardial infarction and stroke. One of the major components of thrombi is platelets activated by hydrogen peroxide (H2O2). H2O2 is known to activate platelets and damage blood vessels and therefore holds great potential as a biomarker of thrombosis. Aspirin has been widely used for the treatment and prevention of vascular diseases. However, aspirin has a short half-life in plasma and is unable to target a thrombus and inhibit the generation of H2O2. In this study, poly(salicylate-co-oxalate) (TT-PSOX) was synthesized as a platform of H2O2-activatable and thrombus-targeting nano-theranostics. TT-PSOX nanoparticles were able to rapidly scavenge H2O2 and release salicylate in a H2O2-triggered manner. TT-PSOX nanoparticles inhibited the expression of tumor necrosis factor-alpha (TNF-α) and soluble CD40 ligand (sCD40L) on activated platelets, demonstrating their intrinsic anti-inflammatory, antiplatelet and antioxidant activities. In mouse models of carotid thrombosis, TT-PSOX nanoparticles specifically targeted the obstructive thrombus, significantly enhanced the fluorescence signal and remarkably suppressed thrombus formation. The novel TT-PSOX nanoparticles offer tremendous potential as platforms of imaging and therapeutic agents for H2O2-associated diseases such as obstructive thrombosis.
Thrombosis is one of the major life-threatening diseases worldwide, causing myocardial infarction and stroke. One of the major components of thrombi is platelets activated by hydrogen peroxide (H2O2). H2O2 is known to activate platelets and damage blood vessels and therefore holds great potential as a biomarker of thrombosis. Aspirin has been widely used for the treatment and prevention of vascular diseases. However, aspirin has a short half-life in plasma and is unable to target a thrombus and inhibit the generation of H2O2. In this study, poly(salicylate-co-oxalate) (TT-PSOX) was synthesized as a platform of H2O2-activatable and thrombus-targeting nano-theranostics. TT-PSOX nanoparticles were able to rapidly scavenge H2O2 and release salicylate in a H2O2-triggered manner. TT-PSOX nanoparticles inhibited the expression of tumor necrosis factor-alpha (TNF-α) and soluble CD40 ligand (sCD40L) on activated platelets, demonstrating their intrinsic anti-inflammatory, antiplatelet and antioxidant activities. In mouse models of carotid thrombosis, TT-PSOX nanoparticles specifically targeted the obstructive thrombus, significantly enhanced the fluorescence signal and remarkably suppressed thrombus formation. The novel TT-PSOX nanoparticles offer tremendous potential as platforms of imaging and therapeutic agents for H2O2-associated diseases such as obstructive thrombosis.