한빛사 논문
Homan Kang1,5, Murui Han2,5, Jie Xue2, Yoonji Baek1, JuOae Chang2, Shuang Hu1, HaYoung Nam2, Min Joo Jo1, Georges El Fakhri1, Michael P. Hutchens3,4, Hak Soo Choi1,* & Jonghan Kim2,*
1 Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
2 Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
3 Anesthesiology and Perioperative Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
4 Portland Veterans Affairs Medical Center, Portland, OR 97239, USA.
5These authors contributed equally: Homan Kang, Murui Han
*Correspondence to Hak Soo Choi or Jonghan Kim
Abstract
Iron chelators have been widely used to remove excess toxic iron from patients with secondary iron overload. However, small molecule-based iron chelators can cause adverse side effects such as infection, gastrointestinal bleeding, kidney failure, and liver fibrosis. Here we report renal clearable nanochelators for iron overload disorders. First, after a singledose intravenous injection, the nanochelator shows favorable pharmacokinetic properties, such as kidney-specific biodistribution and rapid renal excretion (>80% injected dose in 4 h), compared to native deferoxamine (DFO). Second, subcutaneous (SC) administration of nanochelators improves pharmacodynamics, as evidenced by a 7-fold increase in efficiency of urinary iron excretion compared to intravenous injection. Third, daily SC injections of the nanochelator for 5 days to iron overload mice and rats decrease iron levels in serum and liver. Furthermore, the nanochelator significantly reduces kidney damage caused by iron overload without demonstrating DFO’s own nephrotoxicity. This renal clearable nanochelator provides enhanced efficacy and safety.
논문정보
관련 링크
연구자 키워드
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기