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.

Details

Title
Ultrasmall targeted nanoparticles with engineered antibody fragments for imaging detection of HER2-overexpressing breast cancer
Author
Chen, Feng 1   VIAFID ORCID Logo  ; Ma, Kai 2   VIAFID ORCID Logo  ; Madajewski, Brian 1   VIAFID ORCID Logo  ; Zhuang, Li 3 ; Zhang, Li 1 ; Rickert, Keith 3   VIAFID ORCID Logo  ; Marelli, Marcello 3   VIAFID ORCID Logo  ; Yoo, Barney 1 ; Turker, Melik Z 2   VIAFID ORCID Logo  ; Overholtzer, Michael 4 ; Quinn, Thomas P 5 ; Gonen, Mithat 6 ; Zanzonico, Pat 7 ; Tuesca, Anthony 3 ; Bowen, Michael A 3 ; Norton, Larry 8 ; J Anand Subramony 3 ; Wiesner, Ulrich 2 ; Bradbury, Michelle S 9   VIAFID ORCID Logo 

 Department of Radiology, Sloan Kettering Institute for Cancer Research, New York, NY, USA 
 Department of Materials Science & Engineering, Cornell University, Ithaca, NY, USA 
 MedImmune, LLC, Gaithersburg, MD, USA 
 Cell Biology Program, Sloan Kettering Institute for Cancer Research, New York, NY, USA; BCMB Allied Program, Weill Cornell Medical College, New York, NY, USA 
 Department of Biochemistry, University of Missouri, Columbia, MO, USA; Harry S. Truman Veterans’ Hospital, Columbia, MO, USA 
 Department of Epidemiology and Biostatistics, Sloan Kettering Institute for Cancer Research, New York, NY, USA 
 Department of Medical Physics, Sloan Kettering Institute for Cancer Research, New York, NY, USA 
 Department of Medicine & Office of the President, Memorial Sloan Kettering Cancer Center, New York, NY, USA 
 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 
Pages
1-11
Publication year
2018
Publication date
Oct 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2117203872
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.