Tumor Homing Reactive Oxygen Species Nanoparticle for Enhanced Cancer Therapy

Hyeon Yeol Cho, Ahmet Mavi, Sy Tsong Dean Chueng, Thanapat Pongkulapa, Nicholas Pasquale, Hudifah Rabie, Jiyou Han, Jong-Hoon Kim, Tae Hyung Kim, Jeong Woo Choi, Ki Bum Lee

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Multifunctional nanoparticles that carry chemotherapeutic agents can be innovative anticancer therapeutic options owing to their tumor-targeting ability and high drug-loading capacity. However, the nonspecific release of toxic DNA-intercalating anticancer drugs from the nanoparticles has significant side effects on healthy cells surrounding the tumors. Herein, we report a tumor homing reactive oxygen species nanoparticle (THoR-NP) platform that is highly effective and selective for ablating malignant tumors. Sodium nitroprusside (SNP) and diethyldithiocarbamate (DDC) were selected as an exogenous reactive oxygen species (ROS) generator and a superoxide dismutase 1 inhibitor, respectively. DDC-loaded THoR-NP, in combination with SNP treatment, eliminated multiple cancer cell lines effectively by the generation of peroxynitrite in the cells (>95% cell death), as compared to control drug treatments of the same concentration of DDC or SNP alone (0% cell death). Moreover, the magnetic core (ZnFe2O4) of the THoR-NP can specifically ablate tumor cells (breast cancer cells) via magnetic hyperthermia, in conjunction with DDC, even in the absence of any exogenous RS supplements. Finally, by incorporating iRGD peptide moieties in the THoR-NP, integrin-enriched cancer cells (malignant tumors, MDA-MB-231) were effectively and selectively killed, as opposed to nonmetastatic tumors (MCF-7), as confirmed in a mouse xenograft model. Hence, our strategy of using nanoparticles embedded with ROS-scavenger-inhibitor with an exogenous ROS supplement is highly selective and effective cancer therapy.

Original languageEnglish
JournalACS Applied Materials and Interfaces
DOIs
Publication statusPublished - 2019 Jan 1

Keywords

  • cancer therapy
  • magnetic core-shell nanoparticles
  • nanotechnology
  • reactive species
  • tumor targeting

ASJC Scopus subject areas

  • Materials Science(all)

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  • Cite this

    Cho, H. Y., Mavi, A., Chueng, S. T. D., Pongkulapa, T., Pasquale, N., Rabie, H., Han, J., Kim, J-H., Kim, T. H., Choi, J. W., & Lee, K. B. (2019). Tumor Homing Reactive Oxygen Species Nanoparticle for Enhanced Cancer Therapy. ACS Applied Materials and Interfaces. https://doi.org/10.1021/acsami.9b07483