Laboratoire Matière et Systèmes Complexes, UMR 7057 CNRS/Université Paris Diderot, Sorbonne Paris Cité, 10 rue Alice Domon et Léonie Duquet, 75205 Paris Cedex 13, France.
Inserm U970, Paris Cardiovascular Research Center-PARCC/Université Paris-Descartes, Sorbonne Paris Cité, 56 rue Leblanc, 75015 France.
Sci Rep. 2017 Jan 9;7:40075. doi: 10.1038/srep40075.
Metallic nanoparticles have been increasingly suggested as prospective therapeutic nanoplatforms, yet their long-term fate and cellular processing in the body is poorly understood. Here we examined the role of an endogenous iron storage protein - namely the ferritin - in the remediation of biodegradable cobalt ferrite magnetic nanoparticles. Structural and elemental analysis of ferritins close to exogenous nanoparticles within spleens and livers of mice injected in vivo with cobalt ferrite nanoparticles, suggests the intracellular transfer of degradation-derived cobalt and iron, entrapped within endogenous protein cages. In addition, the capacity of ferritin cages to accommodate and store the degradation products of cobalt ferrite nanoparticles was investigated in vitro in the acidic environment mimicking the physiological conditions that are present within the lysosomes. The magnetic, colloidal and structural follow-up of nanoparticles and proteins in the lysosome-like medium confirmed the efficient remediation of nanoparticle-released cobalt and iron ions by ferritins in solution. Metal transfer into ferritins could represent a quintessential process in which biomolecules and homeostasis regulate the local degradation of nanoparticles and recycle their by-products.
金属纳米颗粒作为有前途的治疗性纳米平台越来越受到关注，但它们在体内的长期命运和细胞处理仍知之甚少。在这里，我们研究了一种内源性铁储存蛋白 - 铁蛋白 - 在可生物降解的钴铁氧体磁性纳米颗粒修复中的作用。对注射体内钴铁氧体纳米颗粒的小鼠脾脏和肝脏中接近外源性纳米颗粒的铁蛋白进行结构和元素分析，表明在细胞内转移了降解衍生的钴和铁，被困在内源性蛋白笼内。此外，还在模拟溶酶体中存在的生理条件的酸性环境中，在体外研究了铁蛋白笼容纳和储存钴铁氧体纳米颗粒降解产物的能力。在类溶酶体介质中对纳米颗粒和蛋白质的磁性、胶体和结构进行后续跟踪，证实了铁蛋白溶液中有效修复了纳米颗粒释放的钴和铁离子。金属转移到铁蛋白中可能是生物分子和动态平衡调节纳米颗粒局部降解并回收其副产物的关键过程。
