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Realizing the full potential of iron oxide nanoparticles (IONP) for cancer diagnosis and therapy requires selective tumor cell accumulation. Here, we report a systematic analysis of two key determinants for IONP homing to human breast cancers: (i) particle size and (ii) active vs passive targeting.  In vitro , molecular targeting to the HER2 receptor was the dominant factor driving cancer cell association. In contrast, size was found to be the key determinant of tumor accumulation  in vivo , where molecular targeting increased tumor tissue concentrations for 30 nm but not 100 nm IONP. Similar to the  in vitro  results, PEGylation did not influence  in vivo  IONP biodistribution. Thus, the results reported here indicate that the  in vitro  advantages of molecular targeting may not consistently extend to pre-clinical  in vivo  settings. These observations may have important implications for the design and clinical translation of advanced, multifunctional, IONP platforms.

Tumor Cell Targeting by Iron Oxide Nanoparticles Is Dominated by Different Factors In Vitro versus In Vivo