Biocompatibility of ferritin-based nanoparticles as targeted MRI contrast agents.
Biocompatibility of ferritin-based nanoparticles as targeted MRI contrast agents.
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DOI：
10.1016/j.nano.2016.03.007
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发表时间：
2016-08
期刊：
影响因子：
--
通讯作者：
Bennett KM
中科院分区：
文献类型：
--
作者：
Charlton JR;Pearl VM;Denotti AR;Lee JB;Swaminathan S;Scindia YM;Charlton NP;Baldelomar EJ;Beeman SC;Bennett KM
Ferritin is a naturally occurring iron storage protein, proposed as a clinically relevant nanoparticle with applications as a diagnostic and therapeutic agent. Cationic ferritin is a targeted, injectable contrast agent to measure kidney microstructure with MRI. Here, the toxicity of horse spleen ferritin is assessed as a step to clinical translation. Adult male mice received cationic, native and high dose cationic ferritin (CF, NF, or HDCF) or saline and were monitored for 3 weeks. Transient weight loss occurred in the ferritin groups with no difference in renal function parameters. Ferritin-injected mice demonstrated a lower serum iron 3 weeks after administration. In ferritin-injected animals pre-treated with hydrocortisone, there were no structural or weight differences in the kidneys, liver, lung, heart, or spleen. This study demonstrates a lack of significant detrimental effects of horse-derived ferritin-based nanoparticles at MRI-detectable doses, allowing further exploration of these agents in basic research and clinical diagnostics. Cationic ferritin injected systemically into adult male mice transiently adheres to the glomerular basement membrane and can be noninvasively detected by MRI to count glomeruli and measure morphology as depicted in the inner circle. The outer boxes represent the areas of potential toxicity of either cationic or native ferritin assessed in this study, including kidney effects such as disruption of the glomerular basement membrane in the kidney, iron toxicity in liver and spleen, and the adverse effects of a large horse protein such as inflammation.
