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.
Cell Prolif. 2015 ;48(4):465-74.
Shao XR1, Wei XQ1, Song X2, Hao LY1, Cai XX1, Zhang ZR2, Peng Q1, Lin YF1.
[expand title=”Show Affiliations”]
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
- Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
Up to now, little research has been focussed on discovering how zeta potential independently affects polymeric nanoparticle (NP) cytotoxicity.
Polymeric nanoparticles of gradient zeta potential ranging from -30 mv to +40 mv were fabricated using the same poly-3-hydroxybutyrate-co-3-hydroxyhexanoate (PHBHHx) biopolymer. Interaction forces between nanoparticles and cells were measured by atomic force microscopy (AFM). Cytotoxicity of the nanoparticles to cells was investigated by using MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay.
Four kinds of nanoparticle with similar sizes and gradient zeta potentials, were fabricated. Those with positive surface charges were found to be more toxic than those with negative surface charges. Positively charged nanoparticles or nanoparticles with higher ‘like’ charges, offered higher interaction force with cells.
This work proposes a novel approach for investigating interaction between NPs and cells, and discloses the importance of controlling zeta potential in developing NPs-based formulations in the future.
© 2015 John Wiley & Sons Ltd.
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