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Selective killing of cancer cells by silica nanoparticles due to increased nanoparticle internalization and cellular sensitivity to oxidative stress

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Abstract

Silica Nanoparticles (SNPs) have been found to exhibit higher cytotoxicity to various cancer cells than to normal cells, while the underlying mechanisms are not fully understood. Here, SNPs triggered much higher cytotoxicity and apoptosis rate in human hepatoma HepG2 cells than in their normal counterparts L-02 cells; we thus selected these two cell lines as the cell model to investigate the mechanisms involved in the SNP-induced selective toxicity to cancer cells. Although uptake pathways and cellular trafficking of SNPs in HepG2 and L-02 cells were similar, more SNPs were taken up and accumulated in the mitochondria of cancer cells. After the removal of free SNPs from the culture medium, nanoparticles were excreted from HepG2 cells more effectively in the first 24 h, but 72 h later more SNPs still remained in cancer cells, leading to the continuous drop in cell viability of HepG2 cells. SNPs triggered a higher ROS generation, along with a lower intracellular GSH content and CAT activity in HepG2 cells than in L-02 cells. This could be due to the fact that HepG2 cells showed a much lower tolerance to H2O2-induced oxidative stress and cell death. Thus, the selective cytotoxicity of SNPs towards cancer cells could probably be explained by the higher particle uptake efficiency and cell sensitivity to oxidative stress as observed in HepG2 cells.

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Funding

This study is supported by the National Key Research and Development Program of China (2020YFA0908900), the National Natural Science Foundation of China (31871011).

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Authors and Affiliations

  1. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, People’s Republic of China

    Peng Wang, Tao Shen, Yi Sun, Xinhui Cui & Jiangchao Qian

  2. Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, People’s Republic of China

    Changsheng Liu & Yuan Yuan

Authors
  1. Peng Wang
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  2. Tao Shen
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  3. Yi Sun
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  4. Xinhui Cui
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  5. Changsheng Liu
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  6. Yuan Yuan
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  7. Jiangchao Qian
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Contributions

Peng Wang: Investigation, Original draft.

Tao Shen: Formal analysis, Writing—original draft.

Yi Sun: Data Curation.

Xinhui Cui: Validation.

Changsheng Liu: Resources, Supervision, Funding acquisition.

Yuan Yuan: Methodology, Supervision.

Jiangchao Qian: Conceptualization, Methodology, Writing—review & editing, Funding acquisition.

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Correspondence to Jiangchao Qian.

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Wang, P., Shen, T., Sun, Y. et al. Selective killing of cancer cells by silica nanoparticles due to increased nanoparticle internalization and cellular sensitivity to oxidative stress. J Nanopart Res 25, 13 (2023). https://doi.org/10.1007/s11051-022-05643-9

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