Self-Activating Therapeutic Nanoparticle: A Targeted Tumor Therapy Using Reactive Oxygen Species Self-Generation and Switch-on Drug Release

Rae Hyung Kang, Yumi Kim, Ji Hyeon Kim, Na Hee Kim, Hyun Min Ko, Seung Hyeon Lee, Inseob Shim, Jong Seung Kim, Hyeung Jin Jang, Dokyoung Kim

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

One of the recent advances in nanotechnology within the medical field is the development of a nanoformulation of anticancer drugs or photosensitizers. Cancer cell-specific drug delivery and upregulation of the endogenous level of reactive oxygen species (ROS) are important in precision anticancer treatment. Within our article, we report a new therapeutic nanoformulation of cancer cell targeting using endogenous ROS self-generation without an external initiator and a switch-on drug release (ROS-induced cascade nanoparticle degradation and anticancer drug generation). We found a substantial cellular ROS generation by treating an isothiocyanate-containing chemical and functionalizing it onto the surface of porous silicon nanoparticles (pSiNPs) that are biodegradable and ROS-responsive nanocarriers. Simultaneously, we loaded an ROS-responsive prodrug (JS-11) that could be converted to the original anticancer drug, SN-38, and conducted further surface functionalization with a cancer-targeting peptide, CGKRK. We demonstrated the feasibility as a cancer-targeting and self-activating therapeutic nanoparticle in a pancreatic cancer xenograft mouse model, and it showed a superior therapeutic efficacy through ROS-induced therapy and drug-induced cell death. The work presented is a new concept of a nanotherapeutic and provides a more feasible clinical translational pathway.

Original languageEnglish
Pages (from-to)30359-30372
Number of pages14
JournalACS Applied Materials and Interfaces
Volume13
Issue number26
DOIs
Publication statusPublished - 2021 Jul 7

Keywords

  • cancer therapy
  • drug-delivery system
  • porous silicon nanoparticles
  • reactive oxygen species
  • ROS-responsive prodrug

ASJC Scopus subject areas

  • Materials Science(all)

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