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

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.

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Acknowledgements

We thank Drs. Akilan Palanisami and Mans Broekgaarden for insightful discussions and Drs. Jie Zhao and Danian Cao for their excellent technical expertise. This work was supported by the National Institutes of Health (Nos. K99CA215301 and R00CA215301 to G. O., No. R37CA212187 to K. S., and Nos. P01CA084203, R01CA156177, R01CA160998, S10ODO1232601, and R21CA220143 to T. H.); the Bullock-Wellman Fellowship (G. O.), Science Foundation Ireland and the Irish Research Council (S. C.), and the American Society of Lasers in Surgery and Medicine Research Grant (S. M.).

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Correspondence to Tayyaba Hasan.

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

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Obaid, G., Samkoe, K., Tichauer, K. et al. Is tumor cell specificity distinct from tumor selectivity in vivo? A quantitative NIR molecular imaging analysis of nanoliposome targeting. Nano Res. 14, 1344–1354 (2021). https://doi.org/10.1007/s12274-020-3178-x

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Keywords

  • molecular recognition
  • receptors
  • nanoparticles
  • specificity
  • cancer