Electrostatic interactions favor the binding of positive nanoparticles on cells: A reductive theory

•Positive nanoparticle/cell membrane interactions are privileged.•It is supposedly due to favorable electrostatic interactions.•But in biological media, a protein corona forms and adds a level of complexity.

It is acknowledged that physico-chemical features of nanoparticles have a major impact on their uptake, and especially their surface charge. A widespread observation is that positively charged nanoparticles are more uptaken by cells than neutral or negatively charged nanoparticles. The reason commonly evoked is the favorable electrostatic interactions with negatively charged cell membrane. However, this explanation seems simplistic as it does not take into account a fundamental element: the nanoparticle protein corona. This adds a new level of complexity in the interactions with biological systems that cannot be any more limited to electrostatic binding.

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