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Nano Research

Article Title

Is tumor cell specificity distinct from tumor selectivity in vivo? A quantitative NIR molecular imaging analysis of nanoliposome targeting

Authors

Girgis Obaid, Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA;Department of Bioengineering, University of Texas at Dallas, Richardson, TX 75080, USA
Kimberley Samkoe, Thayer School of Engineering, Dartmouth College, Hanover, NH 037551, USA
Kenneth Tichauer, Armour College of Engineering, Illinois Institute of Technology, Chicago, IL 60616, USA
Shazia Bano, Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
Yeonjae Park, Thayer School of Engineering, Dartmouth College, Hanover, NH 037551, USA
Zachary Silber, Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
Sassan Hodge, Thayer School of Engineering, Dartmouth College, Hanover, NH 037551, USA
Susan Callaghan, Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
Mina Guirguis, Department of Bioengineering, University of Texas at Dallas, Richardson, TX 75080, USA
Srivalleesha Mallidi, Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
Brian Pogue, Thayer School of Engineering, Dartmouth College, Hanover, NH 037551, USA
Tayyaba Hasan, Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA;Division of Health Sciences and Technology, Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02139, USA

Keywords

molecular recognition, receptors, nanoparticles, specificity, cancer

Abstract

The significance and ability for receptor targeted nanoliposomes (tNLs) to bind to their molecular targets in solid tumors in vivo has been questioned, particularly as the efficiency of their tumor accumulation and selectivity is not always predictive of their efficacy or molecular specificity. This study presents, for the first time, in situ near-infrared (NIR) molecular imaging-based quantitation of the in vivo specificity of tNLs for their target receptors, as opposed to tumor selectivity, which includes influences of enhanced tumor permeability and retention. Results show that neither tumor delivery nor selectivity (tumor-to-normal ratio) of cetuximab and IRDye conjugated tNLs correlate with epidermal growth factor receptor (EGFR) expression in U251, U87, and 9L tumors, and in fact underrepresent their imaging-derived molecular specificity by up to 94.2%. Conversely, their in vivo specificity, which we quantify as the concentration of tNL-reported tumor EGFR provided by NIR molecular imaging, correlates positively with EGFR expression levels in vitro and ex vivo (Pearson’s r = 0.92 and 0.96, respectively). This study provides a unique opportunity to address the problematic disconnect between tNL synthesis and in vivo specificity. The findings encourage their continued adoption as platforms for precision medicine, and facilitates intelligent synthesis and patient customization in order to improve safety profiles and therapeutic outcomes.

Publisher

Tsinghua University Press

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