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


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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  1. [1]

    Maeda, H.; Nakamura, H.; Fang, J. The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv. Drug Deliv. Rev. 2013, 65, 71–79.

    CAS  Google Scholar 

  2. [2]

    Obaid, G.; Bano, S.; Mallidi, S.; Broekgaarden, M.; Kuriakose, J.; Silber, Z.; Bulin, A. L.; Wang, Y. C.; Mai, Z. M.; Jin, W. D. et al. Impacting pancreatic cancer therapy in heterotypic in vitro organoids and in vivo tumors with specificity-tuned, NIR-activable photoimmunonanoconjugates: Towards conquering desmoplasia? Nano Lett. 2019, 19, 7573–7587.

    CAS  Google Scholar 

  3. [3]

    Obaid, G.; Chambrier, I.; Cook, M. J.; Russell, D. A. Targeting the oncofetal Thomsen-Friedenreich disaccharide using jacalin-PEG phthalocyanine gold nanoparticles for photodynamic cancer therapy. Angew. Chem., Int. Ed. 2012, 51, 6158–6162.

    CAS  Google Scholar 

  4. [4]

    Obaid, G.; Chambrier, I.; Cook, M. J.; Russell, D. A. Cancer targeting with biomolecules: A comparative study of photodynamic therapy efficacy using antibody or lectin conjugated phthalocyanine-PEG gold nanoparticles. Photochem. Photobiol. Sci. 2015, 14, 737–747.

    CAS  Google Scholar 

  5. [5]

    Bano, S.; Obaid, G.; Swain, J. W. R.; Yamada, M.; Pogue, B. W.; Wang, K.; Hasan, T. NIR Photodynamic destruction of PDAC and HNSCC nodules using triple-receptor-targeted photoimmunonanoconjugates: Targeting heterogeneity in cancer. J. Clin. Med. 2020, 9, 2390.

    CAS  Google Scholar 

  6. [6]

    Schmidt, M. M.; Wittrup, K. D. A modeling analysis of the effects of molecular size and binding affinity on tumor targeting. Mol. Cancer Ther. 2009, 8, 2861–2871.

    CAS  Google Scholar 

  7. [7]

    Han, H.; Davis, M. E. Single-antibody, targeted nanoparticle delivery of camptothecin. Mol. Pharmaceutics 2013, 10, 2558–2567.

    CAS  Google Scholar 

  8. [8]

    Mamot, C.; Drummond, D. C.; Noble, C. O.; Kallab, V.; Guo, Z. X.; Hong, K.; Kirpotin, D. B.; Park, J. W. Epidermal growth factor receptor-targeted immunoliposomes significantly enhance the efficacy of multiple anticancer drugs in vivo. Cancer Res. 2005, 65, 11631–11638.

    CAS  Google Scholar 

  9. [9]

    Bartlett, D. W.; Su, H.; Hildebrandt, I. J.; Weber, W. A.; Davis, M. E. Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging. Proc. Natl. Acad. Sci. USA 2007, 104, 15549–15554.

    CAS  Google Scholar 

  10. [10]

    Kirpotin, D. B.; Drummond, D. C.; Shao, Y.; Shalaby, M. R.; Hong, K.; Nielsen, U. B.; Marks, J. D.; Benz, C. C.; Park, J. W. Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models. Cancer Res. 2006, 66, 6732–6740.

    CAS  Google Scholar 

  11. [11]

    Kotagiri, N.; Sudlow, G. P.; Akers, W. J.; Achilefu, S. Breaking the depth dependency of phototherapy with Cerenkov radiation and low-radiance-responsive nanophotosensitizers. Nat. Nanotechnol. 2015, 10, 370–379.

    CAS  Google Scholar 

  12. [12]

    Dai, Q.; Wilhelm, S.; Ding, D.; Syed, A. M.; Sindhwani, S.; Zhang, Y. W.; Chen, Y. Y.; MacMillan, P.; Chan, W. C. W. Quantifying the ligand-coated nanoparticle delivery to cancer cells in solid tumors. ACS Nano 2018, 12, 8423–8435.

    CAS  Google Scholar 

  13. [13]

    Obaid, G.; Broekgaarden, M.; Bulin, A. L.; Huang, H. C.; Kuriakose, J.; Liu, J.; Hasan, T. Photonanomedicine: A convergence of photodynamic therapy and nanotechnology. Nanoscale 2016, 8, 12471–12503.

    CAS  Google Scholar 

  14. [14]

    Heukers, R.; van Bergen en Henegouwen, P. M. P.; Oliveira, S. Nanobody-photosensitizer conjugates for targeted photodynamic therapy. Nanomed. Nanotechnol. Biol. Med. 2014, 10, 1441–1451.

    CAS  Google Scholar 

  15. [15]

    Nagaya, T.; Nakamura, Y.; Sato, K.; Harada, T.; Choyke, P. L.; Hodge, J. W.; Schlom, J.; Kobayashi, H. Near infrared photoimmunotherapy with avelumab, an anti-programmed death-ligand 1 (PD-L1) antibody. Oncotarget 2017, 8, 8807–8817.

    Google Scholar 

  16. [16]

    Soukos, N. S.; Hamblin, M. R.; Keel, S.; Fabian, R. L.; Deutsch, T. F.; Hasan, T. Epidermal growth factor receptor-targeted immunophotodiagnosis and photoimmunotherapy of oral precancer in vivo. Cancer Res. 2001, 61, 4490–4496.

    CAS  Google Scholar 

  17. [17]

    Kotagiri, N.; Cooper, M. L.; Rettig, M.; Egbulefu, C.; Prior, J.; Cui, G.; Karmakar, P.; Zhou, M. Z.; Yang, X. X.; Sudlow, G. et al. Radionuclides transform chemotherapeutics into phototherapeutics for precise treatment of disseminated cancer. Nat. Commun. 2018, 9, 275.

    Google Scholar 

  18. [18]

    Skovsen, E.; Snyder, J. W.; Lambert, J. D. C.; Ogilby, P. R. Lifetime and diffusion of singlet oxygen in a cell. J. Phys. Chem. B 2005, 109, 8570–8573.

    CAS  Google Scholar 

  19. [19]

    Kessel, D. Photodynamic therapy: Promotion of efficacy by a sequential protocol. J. Porphyr. Phthalocyanines 2016, 20, 302–306.

    CAS  Google Scholar 

  20. [20]

    Rizvi, I.; Nath, S.; Obaid, G.; Ruhi, M. K.; Moore, K.; Bano, S.; Kessel, D.; Hasan, T. A Combination of visudyne and a lipid-anchored liposomal formulation of benzoporphyrin derivative enhances photodynamic therapy efficacy in a 3D model for ovarian cancer. Photochem. Photobiol. 2019, 95, 419–429.

    CAS  Google Scholar 

  21. [21]

    Hudson, R.; Carcenac, M.; Smith, K.; Madden, L.; Clarke, O. J.; Pèlegrin, A.; Greenman, J.; Boyle, R. W. The development and characterisation of porphyrin isothiocyanate-monoclonal antibody conjugates for photoimmunotherapy. Br. J. Cancer 2005, 92, 1442–1449.

    CAS  Google Scholar 

  22. [22]

    Rizvi, I.; Obaid, G.; Bano, S.; Hasan, T.; Kessel, D. Photodynamic therapy: Promoting in vitro efficacy of photodynamic therapy by liposomal formulations of a photosensitizing agent. Lasers Surg. Med. 2018, 50, 499–505.

    Google Scholar 

  23. [23]

    Li, J. C.; Cui, D.; Huang, J. G.; He, S. S.; Yang, Z. B.; Zhang, Y.; Luo, Y.; Pu, K. Y. Organic semiconducting pro-nanostimulants for near-infrared photoactivatable cancer immunotherapy. Angew. Chem., Int. Ed. 2019, 58, 12680–12687.

    CAS  Google Scholar 

  24. [24]

    Cui, D.; Huang, J. G.; Zhen, X.; Li, J. C.; Jiang, Y. Y.; Pu, K. Y. A semiconducting polymer nano-prodrug for hypoxia-activated photodynamic cancer therapy. Angew. Chem., Int. Ed. 2019, 58, 5920–5924.

    CAS  Google Scholar 

  25. [25]

    ClinicalTrials. gov Identifier: NCT03076372[Online]. (accessed July, 2020).

  26. [26]

    ClinicalTrials. gov Identifier: NCT02369198[Online]. (accessed July, 2020).

  27. [27]

    ClinicalTrials. gov Identifier: NCT01304797[Online]. (accessed July, 2020).

  28. [28]

    ClinicalTrials. gov Identifier: NCT01517464[Online]. (accessed July, 2020).

  29. [29]

    Harari, P. M.; Huang, S. M. Head and neck cancer as a clinical model for molecular targeting of therapy: Combining EGFR blockade with radiation. Int. J. Radiat. Oncol. Biol. Phys. 2001, 49, 427–433.

    CAS  Google Scholar 

  30. [30]

    Lee, H. J.; Seo, A. N.; Kim, E. J.; Jang, M. H.; Kim, Y. J.; Kim, J. H.; Kim, S. W.; Ryu, H. S.; Park, I. A.; Im, S. A. et al. Prognostic and predictive values of EGFR overexpression and EGFR copy number alteration in HER2-positive breast cancer. Br. J. Cancer 2015, 112, 103–111.

    CAS  Google Scholar 

  31. [31]

    Hashmi, A. A.; Naz, S.; Hashmi, S. K.; Irfan, M.; Hussain, Z. F.; Khan, E. Y.; Asif, H.; Faridi, N. Epidermal Growth Factor Receptor (EGFR) overexpression in triple-negative breast cancer: Association with clinicopathologic features and prognostic parameters. Surg. Exp. Pathol. 2019, 2, 6.

    Google Scholar 

  32. [32]

    Shinojima, N.; Tada, K.; Shiraishi, S.; Kamiryo, T.; Kochi, M.; Nakamura, H.; Makino, K.; Saya, H.; Hirano, H.; Kuratsu, J. I. et al. Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme. Cancer Res. 2003, 63, 6962–6970.

    CAS  Google Scholar 

  33. [33]

    Tichauer, K. M.; Samkoe, K. S.; Sexton, K. J.; Hextrum, S. K.; Yang, H. H.; Klubben, W. S.; Gunn, J. R.; Hasan, T.; Pogue, B. W. In vivo quantification of tumor receptor binding potential with dual-reporter molecular imaging. Mol. Imaging Biol. 2012, 14, 584–592.

    Google Scholar 

  34. [34]

    Samkoe, K. S.; Tichauer, K. M.; Gunn, J. R.; Wells, W. A.; Hasan, T.; Pogue, B. W. Quantitative in vivo immunohistochemistry of epidermal growth factor receptor using a receptor concentration imaging approach. Cancer Res. 2014, 74, 7465–7474.

    CAS  Google Scholar 

  35. [35]

    Rasband, W. S. ImageJ, U. S. National institutes of health, Bethesda, Maryland, USA, 1997–2018 [Online].

  36. [36]

    Tichauer, K. M.; Samkoe, K. S.; Sexton, K. J.; Gunn, J. R.; Hasan, T.; Pogue, B. W. Improved tumor contrast achieved by single time point dual-reporter fluorescence imaging. J. Biomed. Opt. 2012, 17, 066001.

    Google Scholar 

  37. [37]

    Maruyama, K.; Takizawa, T.; Yuda, T.; Kennel, S. J.; Huang, L.; Iwatsuru, M. Targetability of novel immunoliposomes modified with amphipathic poly(ethylene glycol)s conjugated at their distal terminals to monoclonal antibodies. Biochim. Biophys. Acta 1995, 1234, 74–80.

    Google Scholar 

  38. [38]

    Harding, J. A.; Engbers, C. M.; Newman, M. S.; Goldstein, N. I.; Zalipsky, S. Immunogenicity and pharmacokinetic attributes of poly(ethylene glycol)-grafted immunoliposomes. Biochim. Biophys. Acta 1997, 1327, 181–192.

    CAS  Google Scholar 

  39. [39]

    Shokeen, M.; Pressly, E. D.; Hagooly, A.; Zheleznyak, A.; Ramos, N.; Fiamengo, A. L.; Welch, M. J.; Hawker, C. J.; Anderson, C. J. Evaluation of multivalent, functional polymeric nanoparticles for imaging applications. ACS Nano 2011, 5, 738–747.

    CAS  Google Scholar 

  40. [40]

    Gabizon, A.; Shmeeda, H.; Barenholz, Y. Pharmacokinetics of pegylated liposomal doxorubicin: Review of animal and human studies. Clin. Pharmacokinet. 2003, 42, 419–436.

    CAS  Google Scholar 

  41. [41]

    Corbet, C.; Feron, O. Tumour acidosis: From the passenger to the driver’s seat. Nat. Rev. Cancer 2017, 17, 577–593.

    CAS  Google Scholar 

  42. [42]

    Patel, D.; Lahiji, A.; Patel, S.; Franklin, M.; Jimenez, X.; Hicklin, D. J.; Kang, X. Q. Monoclonal antibody cetuximab binds to and down-regulates constitutively activated epidermal growth factor receptor vIII on the cell surface. Anticancer Res. 2007, 27, 3355–3366.

    CAS  Google Scholar 

  43. [43]

    Semple, S. C.; Chonn, A.; Cullis, P. R. Interactions of liposomes and lipid-based carrier systems with blood proteins: Relation to clearance behaviour in vivo. Adv. Drug Deliv. Rev. 1998, 32, 3–17.

    CAS  Google Scholar 

  44. [44]

    Gonzalez-Quintela, A.; Alende, R.; Gude, F.; Campos, J.; Rey, J.; Meijide, L. M.; Fernandez-Merino, C.; Vidal, C. Serum levels of immunoglobulins (IgG, IgA, IgM) in a general adult population and their relationship with alcohol consumption, smoking and common metabolic abnormalities. Clin. Exp. Immunol. 2008, 151, 42–50.

    CAS  Google Scholar 

  45. [45]

    Peng, X. Z.; Chen, H. X.; Draney, D. R.; Volcheck, W.; Schutz-Geschwender, A.; Olive, D. M. A nonfluorescent, broad-range quencher dye for Förster resonance energy transfer assays. Anal. Biochem. 2009, 388, 220–228.

    CAS  Google Scholar 

  46. [46]

    Lin, H. Y.; Zhang, R. X.; Gunn, J. R.; Esipova, T. V.; Vinogradov, S.; Gladstone, D. J.; Jarvis, L. A.; Pogue, B. W. Comparison of Cherenkov excited fluorescence and phosphorescence molecular sensing from tissue with external beam irradiation. Phys. Med. Biol. 2016, 61, 3955–3968.

    CAS  Google Scholar 

  47. [47]

    Obaid, G.; Spring, B. Q.; Bano, S.; Hasan, T. Activatable clinical fluorophore-quencher antibody pairs as dual molecular probes for the enhanced specificity of image-guided surgery. J. Biomed. Opt. 2017, 22, 121607.

    Google Scholar 

  48. [48]

    Spring, B. Q.; Bryan Sears, R.; Zheng, L. Z.; Mai, Z. M.; Watanabe, R.; Sherwood, M. E.; Schoenfeld, D. A.; Pogue, B. W.; Pereira, S. P.; Villa, E. et al. A photoactivable multi-inhibitor nanoliposome for tumour control and simultaneous inhibition of treatment escape pathways. Nat. Nanotechnol. 2016, 11, 378–387.

    CAS  Google Scholar 

  49. [49]

    Pastore, S.; Mascia, F.; Mariani, V.; Girolomoni, G. The epidermal growth factor receptor system in skin repair and inflammation. J. Invest. Dermatol. 2008, 128, 1365–1374.

    CAS  Google Scholar 

  50. [50]

    Minder, P.; Zajac, E.; Quigley, J. P.; Deryugina, E. I. EGFR regulates the development and microarchitecture of intratumoral angiogenic vasculature capable of sustaining cancer cell intravasation. Neoplasia 2015, 17, 634–649.

    CAS  Google Scholar 

  51. [51]

    van Cruijsen, H.; Giaccone, G.; Hoekman, K. Epidermal growth factor receptor and angiogenesis: Opportunities for combined anticancer strategies. Int. J. Cancer 2005, 117, 883–888.

    CAS  Google Scholar 

  52. [52]

    Amin, D. N.; Hida, K.; Bielenberg, D. R.; Klagsbrun, M. Tumor endothelial cells express epidermal growth factor receptor (EGFR) but not ErbB3 and are responsive to EGF and to EGFR kinase inhibitors. Cancer Res. 2006, 66, 2173–2180.

    CAS  Google Scholar 

  53. [53]

    Tundidor, Y.; García-Hernández, C. P.; Pupo, A.; Infante, Y. C.; Rojas, G. Delineating the functional map of the interaction between nimotuzumab and the epidermal growth factor receptor. MABs 2014, 6, 1013–1025.

    Google Scholar 

  54. [54]

    Sato, J. D.; Kawamoto, T.; Le, A. D.; Mendelsohn, J.; Polikoff, J.; Sato, G. H. Biological effects in vitro of monoclonal antibodies to human epidermal growth factor receptors. Mol. Biol. Med. 1983, 1, 511–529.

    CAS  Google Scholar 

  55. [55]

    Hoeben, B. A. W.; Molkenboer-Kuenen, J. D. M.; Oyen, W. J. G.; Peeters, W. J. M.; Kaanders, J. H. A. M.; Bussink, J.; Boerman, O. C. Radiolabeled cetuximab: Dose optimization for epidermal growth factor receptor imaging in a head-and-neck squamous cell carcinoma model. Int. J. Cancer 2011, 129, 870–878.

    CAS  Google Scholar 

  56. [56]

    He, X. Z.; Cruz, J. L.; Joseph, S.; Pett, N.; Chew, H. Y.; Tuong, Z. K.; Okano, S.; Kelly, G.; Veitch, M.; Simpson, F. et al. Characterization of 7A7, an anti-mouse EGFR monoclonal antibody proposed to be the mouse equivalent of cetuximab. Oncotarget 2018, 9, 12250–12260.

    Google Scholar 

  57. [57]

    Yuan, F.; Leunig, M.; Huang, S. K.; Berk, D. A.; Papahadjopoulos, D.; Jain, R. K. Mirovascular permeability and interstitial penetration of sterically stabilized (stealth) liposomes in a human tumor xenograft. Cancer Res. 1994, 54, 3352–3356.

    CAS  Google Scholar 

  58. [58]

    Drummond, D. C.; Meyer, O.; Hong, K.; Kirpotin, D. B.; Papahadjopoulos, D. Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors. Pharmacol. Rev. 1999, 51, 691–743.

    CAS  Google Scholar 

  59. [59]

    Juweid, M.; Neumann, R.; Paik, C.; Perez-Bacete, M. J.; Sato, J.; van Osdol, W.; Weinstein, J. N. Micropharmacology of monoclonal antibodies in solid tumors: Direct experimental evidence for a binding site barrier. Cancer Res. 1992, 52, 5144–5153.

    CAS  Google Scholar 

  60. [60]

    Baker, J. H. E.; Lindquist, K. E.; Huxham, L. A.; Kyle, A. H.; Sy, J. T.; Minchinton, A. I. Direct visualization of heterogeneous extravascular distribution of trastuzumab in human epidermal growth factor receptor type 2 overexpressing xenografts. Clin. Cancer Res. 2008, 14, 2171–2179.

    CAS  Google Scholar 

  61. [61]

    Obaid, G.; Jin, W. D.; Bano, S.; Kessel, D.; Hasan, T. Nanolipid formulations of benzoporphyrin derivative: Exploring the dependence of nanoconstruct photophysics and photochemistry on their therapeutic index in ovarian cancer cells. Photochem. Photobiol. 2019, 95, 364–377.

    CAS  Google Scholar 

  62. [62]

    Snyder, J. W.; Greco, W. R.; Bellnier, D. A.; Vaughan, L.; Henderson, B. W. Photodynamic therapy: A means to enhanced drug delivery to tumors. Cancer Res. 2003, 63, 8126–8131.

    CAS  Google Scholar 

  63. [63]

    Huang, H. C.; Rizvi, I.; Liu, J.; Anbil, S.; Kalra, A.; Lee, H.; Baglo, Y.; Paz, N.; Hayden, D.; Pereira, S. et al. Photodynamic priming mitigates chemotherapeutic selection pressures and improves drug delivery. Cancer Res. 2018, 78, 558–571.

    CAS  Google Scholar 

  64. [64]

    Overchuk, M.; Zheng, G. Overcoming obstacles in the tumor microenvironment: Recent advancements in nanoparticle delivery for cancer theranostics. Biomaterials 2018, 156, 217–237.

    CAS  Google Scholar 

  65. [65]

    Muchekehu, R.; Liu, D. G.; Horn, M.; Campbell, L.; Del Rosario, J.; Bacica, M.; Moskowitz, H.; Osothprarop, T.; Dirksen, A.; Doppalapudi, V. et al. The effect of molecular weight, PK, and valency on tumor biodistribution and efficacy of antibody-based drugs. Transl. Oncol. 2013, 6, 562–572.

    Google Scholar 

  66. [66]

    Zimpel, A.; Al Danaf, N.; Steinborn, B.; Kuhn, J.; Hohn, M.; Bauer, T.; Hirschle, P.; Schrimpf, W.; Engelke, H.; Wagner, E. et al. Coordinative binding of polymers to metal-organic framework nanoparticles for control of interactions at the biointerface. ACS Nano 2019, 13, 3884–3895.

    CAS  Google Scholar 

  67. [67]

    Sun, H. P.; Su, J. H.; Meng, Q. S.; Yin, Q.; Chen, L. L.; Gu, W. W.; Zhang, P. C.; Zhang, Z. W.; Yu, H. J.; Wang, S. L. et al. Cancer-cell-biomimetic nanoparticles for targeted therapy of homotypic tumors. Adv. Mater. 2016, 28, 9581–9588.

    CAS  Google Scholar 

  68. [68]

    Chen, Z.; Zhao, P. F.; Luo, Z. Y.; Zheng, M. B.; Tian, H.; Gong, P.; Gao, G. H.; Pan, H.; Liu, L. L.; Ma, A. Q. et al. Cancer cell membrane-biomimetic nanoparticles for homologous-targeting dual-modal imaging and photothermal therapy. ACS Nano 2016, 10, 10049–10057.

    CAS  Google Scholar 

  69. [69]

    Lazarovits, J.; Chen, Y. Y.; Song, F. Y.; Ngo, W.; Tavares, A. J.; Zhang, Y. N.; Audet, J.; Tang, B.; Lin, Q. C.; Tleugabulova, M. C. et al. Synthesis of patient-specific nanomaterials. Nano Lett. 2019, 19, 116–123.

    CAS  Google Scholar 

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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).

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  • molecular recognition
  • receptors
  • nanoparticles
  • specificity
  • cancer