Novel platinum therapeutics induce rapid cancer cell death through triggering intracellular ROS storm

Yongbin Liu, Dongfang Yu, Xueying Ge, Lingyi Huang, Ping Ying Pan, Haifa Shen, Roderic I. Pettigrew, Shu Hsia Chen, Junhua Mai

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Induction of reactive oxygen species (ROS) production in cancer cells plays a critical role for cancer treatment. However, therapeutic efficiency remains challenging due to insufficient ROS production of current ROS inducers. We designed a novel platinum (Pt)-based drug named “carrier-platin” that integrates ultrasmall Pt-based nanoparticles uniformly confined within a poly(amino acids) carrier. Carrier-platin dramatically triggered a burst of ROS in cancer cells, leading to cancer cell death as quick as 30 min. Unlike traditional Pt-based drugs which induce cell apoptosis through DNA intercalation, carrier-platin with superior ROS catalytic activities induces a unique pattern of cancer cell death that is neither apoptosis nor ferroptosis and operates independently of DNA damage. Importantly, carrier-platin demonstrates superior anti-tumor efficacy against a broad spectrum of cancers, particularly those with multidrug resistance, while maintaining minimal systemic toxicity. Our findings reveal a distinct mechanism of action of Pt in cancer cell eradication, positioning carrier-platin as a novel category of anti-cancer chemotherapeutics.

Original languageEnglish (US)
Article number122835
JournalBiomaterials
Volume314
Early online dateSep 11 2024
DOIs
StateE-pub ahead of print - Sep 11 2024

Keywords

  • Chemotherapy
  • Drug resistance
  • Platinum
  • Reactive oxygen species
  • Reactive Oxygen Species/metabolism
  • Humans
  • Apoptosis/drug effects
  • Platinum/chemistry
  • Neoplasms/drug therapy
  • Antineoplastic Agents/pharmacology
  • Drug Carriers/chemistry
  • Animals
  • Mice, Nude
  • Nanoparticles/chemistry
  • Cell Line, Tumor
  • Cell Death/drug effects
  • Mice

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Ceramics and Composites
  • Biomaterials
  • Mechanics of Materials

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