Ultrasmall targeted nanoparticles with engineered antibody fragments for imaging detection of HER2-overexpressing breast cancer

Feng Chen, Kai Ma, Brian Madajewski, Li Zhuang, Li Zhang, Keith Rickert, Marcello Marelli, Barney Yoo, Melik Z. Turker, Michael Overholtzer, Thomas P. Quinn, Mithat Gonen, Pat Zanzonico, Anthony Tuesca, Michael A. Bowen, Larry Norton, J. Anand Subramony (), Ulrich Wiesner () and Michelle S. Bradbury ()
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Feng Chen: Sloan Kettering Institute for Cancer Research
Kai Ma: Cornell University
Brian Madajewski: Sloan Kettering Institute for Cancer Research
Li Zhuang: MedImmune, LLC
Li Zhang: Sloan Kettering Institute for Cancer Research
Keith Rickert: MedImmune, LLC
Marcello Marelli: MedImmune, LLC
Barney Yoo: Sloan Kettering Institute for Cancer Research
Melik Z. Turker: Cornell University
Michael Overholtzer: Sloan Kettering Institute for Cancer Research
Thomas P. Quinn: University of Missouri
Mithat Gonen: Sloan Kettering Institute for Cancer Research
Pat Zanzonico: Sloan Kettering Institute for Cancer Research
Anthony Tuesca: MedImmune, LLC
Michael A. Bowen: MedImmune, LLC
Larry Norton: Memorial Sloan Kettering Cancer Center
J. Anand Subramony: MedImmune, LLC
Ulrich Wiesner: Cornell University
Michelle S. Bradbury: Sloan Kettering Institute for Cancer Research

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-06271-5

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