Independent effect of polymeric nanoparticle zeta potential /surface charge, on their cytotoxicity and affinity to cells

Nanoparticles have shown great potentials in drug delivery, diagnosis and therapeutics. However, comprehensive understanding of the effect of nanoparticle zeta potential on its interaction with cells is still lack although such interaction has substantial impacts on nanoparticles efficacy. In this present work, we aim to investigate how nanoparticle zeta potential affects its cytotoxicity and disclose the underlying mechanisms by quantifying the interaction force between cells and nanoparticles via atom force microscopy (AFM). Four kinds of nanoparticles that possessed similar sizes around 230 nm and gradient zeta potentials ranging from -30 mv to +40 mv were fabricated. The cytotoxicity of these nanoparticles was found to be zeta potential-dependent. The nanoparticles  possessing positive surface charges were more toxic than negative nanoparticles, and the nanoparticles possessing higher like charges led to higher cytotoxicity. AFM showed that the positively charged nanoparticles or the nanoparticles with higher like charges had significantly higher interaction force to cells. The interaction force indicated the affinity to cells and could be the main reason of nanoparticles to induce cytotoxicity. This is the first report investigating the independent effect of nanoparticles zeta potential on its cytotoxicity and cellular affinity. Our findings suggest that in practical application, negative nanoparticles would be better for delivering general agents for diagnosis and therapy. On the other hand, positive nanoparticles would be better for delivering anti-tumor agents for chemotherapy. This work proposes a novel approach to investigate the cellular affinity of nanoparticles and demonstrates the importance of controlling zeta potential in practical use of nanoparticles.