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Abstract
Controlling the biodistribution of nanoparticles upon intravenous injection is the key to achieving target specificity. One of the impediments in nanoparticle-based tumor targeting is the inability to limit the trafficking of nanoparticles to liver and other organs leading to smaller accumulated amounts in tumor tissues, particularly via passive targeting. Here we overcome both these challenges by designing nanoparticles that combine the specificity of antibodies with favorable particle biodistribution profiles, while not exceeding the threshold for renal filtration as a combined vehicle. To that end, ultrasmall silica nanoparticles are functionalized with anti-human epidermal growth factor receptor 2 (HER2) single-chain variable fragments to exhibit high tumor-targeting efficiency and efficient renal clearance. This ultrasmall targeted nanotheranostics/nanotherapeutic platform has broad utility, both for imaging a variety of tumor tissues by suitably adopting the targeting fragment and as a potentially useful drug delivery vehicle.
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1 Department of Radiology, Sloan Kettering Institute for Cancer Research, New York, NY, USA
2 Department of Materials Science & Engineering, Cornell University, Ithaca, NY, USA
3 MedImmune, LLC, Gaithersburg, MD, USA
4 Cell Biology Program, Sloan Kettering Institute for Cancer Research, New York, NY, USA; BCMB Allied Program, Weill Cornell Medical College, New York, NY, USA
5 Department of Biochemistry, University of Missouri, Columbia, MO, USA; Harry S. Truman Veterans’ Hospital, Columbia, MO, USA
6 Department of Epidemiology and Biostatistics, Sloan Kettering Institute for Cancer Research, New York, NY, USA
7 Department of Medical Physics, Sloan Kettering Institute for Cancer Research, New York, NY, USA
8 Department of Medicine & Office of the President, Memorial Sloan Kettering Cancer Center, New York, NY, USA
9 Department of Radiology, Sloan Kettering Institute for Cancer Research, New York, NY, USA; Molecular Pharmacology Program, Sloan Kettering Institute for Cancer Research, New York, NY, USA