2133 Nanomedicine (Lond.) (2015) 10(14), 2133–2137 ISSN 1743-5889 part of Journal Watch 10.2217/NNM.15.98 © 2015 Future Medicine Ltd Cleaning blood with functionalized nanoparticles Evaluation of: Kang JH, Super M, Wing Yung C et al. An extracorporeal blood-cleansing device for sepsis therapy. Nat. Med. 20(10), 1211–1216 (2014). Rapid removal of pathogens from the blood is crucial for the treatment of sepsis. Cur- rent sepsis therapy involves the use of broad- spectrum antibiotics. Due to their lack of specificity against the source pathogens, the mortality rates in sepsis patients increase dra- matically for every hour before the correct therapy is administered [1] . Innovative treat- ment strategies are therefore urgently needed, particularly in the light of antibiotic-resistant micro-organisms. Addressing this clinical need, Kang et al. developed a blood-cleansing device (bio- spleen) for pathogen removal from infected blood. For the capture of pathogens, strepta- vidin-coated superparamagnetic nanobeads were conjugated with mannose-binding lec- tin, a broad-spectrum opsonin. To ensure complication-free procedure, mannose- binding lectin was genetically engineered to delete its collagen-helix domain which medi- ates complement binding and coagulation activation [2] . The remaining carbohydrate recognition domain was fused to Fc fragment of human IgG1 and biotinylated to allow conjugation with magnetic nanobeads. For pathogen removal, magnetic opsonins were extracorporally added to the infected blood and incubated before passing through the biospleen separation unit containing two microfluidic channels: blood channel with high-flow rate and slow-flow saline channel. Open rectangular slits provided exchange between the blood channel and the saline channel, mimicking sinusoid slits. Upon passing the biospleen separation unit with magnets positioned above the sinusoid chan- nel, the magnetically opsonized pathogens were attracted through the open slits into the saline channel and discarded. In the proof-of-feasibility studies, a single pass through the blood-cleansing device removed the majority of anaerobic, aerobic and mixed pathogens from experimentally infected whole blood. In the intraperitoneally infected rats, the device removed >90% of Staphylococcus aureus or Escherichia coli from the blood within 1 h. Reduction of blood pathogen level resulted in a decreased patho- gen load and inflammatory cell infiltration in the lungs, spleen and kidneys. Additionally, the levels of inflammatory cytokines and of cell-free toxic hemoglobin were dramatically reduced upon treatment. Consequently, in a rat model of acute endotoxemic shock, the survival upon injection of lethal doses of lipo- polysaccharide was significantly improved by the blood cleansing (survival rate of 14% in untreated group vs 89% in treatment group). In parallel, the normal numbers of infiltrat- ing leukocytes in the lungs and other organs were restored, and clinical distress symptoms such as respiratory rate and temperature were alleviated within 5 h of treatment. In summary, the biospleen device in com- bination with magnetic nanobeads func- tionalized with opsonin represents a prom- ising approach to simultaneous removal of pathogens and endotoxins. Importantly, this method does not require pathogen identifica- tion in the lengthy blood cultures and allows repeated cleansing of the whole blood volume within a short time, without activating coag- ulation or altering blood composition. This Recent nanomedicine articles of outstanding interest: nanoparticle functionalization for disease diagnostics and therapy Christina Janko 1 , Marina Pöttler 1 , Ralf P Friedrich 1 , Stefan Lyer 1 , Iwona Cicha 1 & Christoph Alexiou* ,1 1 ENT-Department, Section of Experimental Oncology & Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung- Professorship for Nanomedicine, University Hospital Erlangen, Glueckstr. 10a, 91054 Erlangen, Germany *Author for correspondence: c.alexiou@web.de For reprint orders, please contact: reprints@futuremedicine.com