Renal Clearance of C•spec™ particles in Mice

March 12, 2009

“Highly sensitive and specific probes and molecular imaging strategies are critical to ensure the earliest possible detection of a tumor and timely response
to treatment.”


  -- Michelle Bradbury, MD, PhD

Study author, Memorial Sloan-Kettering Cancer Center, NYC, NY

A collaborative effort among researchers at HST, Cornell University and Memorial Sloan-Kettering Cancer Center (MSKCC) has resulted in the development of C•spec™ particles capable of clearance from the body via the kidneys (Nano Letters Article). This milestone paves the way for the use of the C•spec™ platform for in vivo imaging applications and potential translation to the clinical space. These particles were designed with three key features in mind: low toxicity, high brightness and rapid clearance from the body. Competitive technologies such as quantum dots are based on toxic heavy metals such as cadmium and lead. The silica-based C•spec™ particles minimize potential toxicity, while achieving high brightness levels due to the beneficial interactions between the dye molecules and the silica matrix. Renal clearance is the method of choice for most drugs because it is rapid and specific, but requires that the imaging agent’s diameter be less than 7 nm and that its surface charge be neutral. Working with researchers in the Wiesner group at Cornell, HST scientists produced C•spec™ particles down to 3.3 nm diameter (10x smaller than previously thought possible) with low polydispersity and neutral organic coatings and were radiolabeled for combined optical-PET imaging. These particles encapsulated dyes with absorption and emission peaks in the near-infrared. The C•spec™ particles were tested in nude mice and found to rapidly clear the bloodstream (24-48 hrs). The particles were visualized by in vivo whole body fluorescence imaging in the bladder as shown above. Throughout the study, no adverse effects were found in mice exposed to particles of varying size and concentration. This work demonstrates the promise of C•spec™ architecture as a clinical platform to address the need for bright NIR fluorescence with biocompatible, easily-functionalized and inert particles. Nano Letters Article Sloan-Kettering Press Release Cornell Chronicle Articlehttp://pubs.acs.org/doi/abs/10.1021/nl803405hhttp://pubs.acs.org/doi/abs/10.1021/nl803405hhttp://www.mskcc.org/mskcc/html/89635.cfmhttp://www.news.cornell.edu/stories/Feb09/dots.cancer.ws.htmlshapeimage_7_link_0shapeimage_7_link_1shapeimage_7_link_2shapeimage_7_link_3