Hsu Jessica C, Cruz Emma D, Lau Kristen C, Bouché Mathilde, Kim Johoon, Maidment Andrew D A, Cormode David P
Department of Radiology, University of Pennsylvania 3400 Spruce St, 1 Silverstein, Philadelphia, PA 19104, USA.
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Chem Mater. 2019 Oct 8;31(19):7845-7854. doi: 10.1021/acs.chemmater.9b01750. Epub 2019 Sep 11.
Significant effort has been focused on developing renally-clearable nanoparticle agents since efficient renal clearance is important for eventual clinical translation. Silver sulfide nanoparticles (AgS-NP) have recently been identified as contrast agents for dual energy mammography, computed tomography (CT) and fluorescence imaging and probes for drug delivery and photothermal therapy with good biocompatibility. However, most AgS-NP reported to date are not renally excretable and are observed to accumulate and remain in the reticuloendothelial system (RES) organs, liver and spleen, for a long time, which could negatively impact their likelihood for translation. Herein, we present renally-clearable, 3.1 nm AgS-NP with 85% of the injected dose (ID) being excreted within 24 hours of intravenous injection, which is amongst the best clearance of similarly sized nanoparticles reported thus far (mostly between 20-75% of ID). The urinary excretion and low RES accumulation of these nanoparticles in mice were indicated by in vivo CT imaging and biodistribution analysis. In summary, these ultrasmall AgS-NP can be effectively eliminated via urine and have high translational potential for various biomedical applications.
由于有效的肾脏清除对于最终的临床转化很重要,因此人们一直致力于开发可通过肾脏清除的纳米颗粒制剂。硫化银纳米颗粒(AgS-NP)最近已被确定为用于双能乳腺摄影、计算机断层扫描(CT)和荧光成像的造影剂,以及用于药物递送和光热治疗的探针,具有良好的生物相容性。然而,迄今为止报道的大多数AgS-NP都不能通过肾脏排泄,并且被观察到会在网状内皮系统(RES)器官、肝脏和脾脏中长时间积累并留存,这可能会对它们的转化可能性产生负面影响。在此,我们展示了可通过肾脏清除的3.1纳米AgS-NP,静脉注射后24小时内,85%的注射剂量(ID)可被排泄,这是迄今为止报道的类似尺寸纳米颗粒中最好的清除率之一(大多在ID的20%-75%之间)。体内CT成像和生物分布分析表明了这些纳米颗粒在小鼠体内的尿液排泄和低RES积累。总之,这些超小的AgS-NP可以通过尿液有效清除,并且在各种生物医学应用中具有很高的转化潜力。