Research Article

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2021, 14(5): 1344–1354

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https://doi.org/10.1007/s12274-020-3178-x

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

Girgis Obaid1,2,†,§, Kimberley Samkoe3,§, Kenneth Tichauer4, Shazia Bano1, Yeonjae Park3, Zachary Silber1, Sassan Hodge3, Susan Callaghan1, Mina Guirguis2, Srivalleesha Mallidi1,‡, Brian Pogue3, and Tayyaba Hasan1,5 (✉)

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1 Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
2 Department of Bioengineering, University of Texas at Dallas, Richardson, TX 75080, USA
3 Thayer School of Engineering, Dartmouth College, Hanover, NH 037551, USA
4 Armour College of Engineering, Illinois Institute of Technology, Chicago, IL 60616, USA
5 Division of Health Sciences and Technology, Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Present address: Department of Bioengineering, University of Texas at Dallas, Richardson, TX 75080, USA
Present address: Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA
§ Girgis Obaid and Kimberley Samkoe contributed equally to the study.

Keywords: molecular recognition, receptors, nanoparticles, specificity, cancer
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  • Abstract
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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.
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Is tumor cell specificity distinct from tumor selectivity in vivo? A quantitative NIR molecular imaging analysis of nanoliposome targeting. Nano Res. 2021, 14(5): 1344–1354 https://doi.org/10.1007/s12274-020-3178-x

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