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Relationship of the surface physicochemical characteristics of nanoparticles with their interactions with biological entities may provide critical information for nanomedicinal application. Here, we report the systematic synthesis of sub-50 nm carbon nanoparticles (CNP) presenting neutral, anionic, and cationic surface functionalities. A subset of CNPs with ~10, 20, and 40 nm hydrodynamic sizes were synthesized with neutral surface headgroups. For the first time, the cellular internalization of these CNPs was systematically quantified in various stages of breast cancer cells (early, late, and metastatic), thereby providing a parametric assessment of charge and size effects. Distinct activities were observed when these systems interacted with cancer cells in various stages. Our results indicated that metastatic breast cancer could be targeted by a nanosystem presenting anionic phosphate groups. On the contrary, for patients in late stage of cancer, drugs could be delivered with sulfonate functionalized carbon nanoparticles, which have higher probability of intracellular transport. This study will facilitate the better understanding of nanoparticle–biological entity interaction, and the integration of this knowledge with pathophysiology would promote the engineering of nanomedicine with superior likelihoods of crossing the endocytic "barrier" for drug delivery inside cancerous cells.
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