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

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.

• Authors: 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, Michelle S Bradbury
• Journal: Nature communications (Nat Commun) Vol. 9 Issue 1 Pg. 4141 (10 08 2018) ISSN: 2041-1723 [Electronic] England
• PMID: 30297810 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Single-Chain Antibodies
• Silicon Dioxide
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Animals
• Breast Neoplasms (diagnostic imaging, metabolism, prevention & control)
• Cell Line, Tumor
• Drug Delivery Systems (methods)
• Drug Liberation
• Female
• Humans
• Mice
• Nanoparticles (administration & dosage, chemistry)
• Particle Size
• Positron-Emission Tomography
• Receptor, ErbB-2 (antagonists & inhibitors, immunology, metabolism)
• Silicon Dioxide (chemistry)
• Single-Chain Antibodies (administration & dosage, chemistry, pharmacokinetics)
• Xenograft Model Antitumor Assays