Fe3+ mediated shikonin and PPA coloaded liposomes induce robust immunogenic cell death by integrating ROS enhancement

Peng Xue1, Jinbo Li1, Jia Song1

  • 1Wuya College of Innovation, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.

Insights

This study introduces a novel liposome (LipoPS) that combines Pyropheophorbide-alpha and shikonin to enhance cancer therapy. LipoPS effectively boosts reactive oxygen species (ROS) and immune response, amplifying antitumor effects.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Immunotherapy

Background:

  • Reactive oxygen species (ROS) play a dual role in cancer, inducing oxidative stress and triggering antitumor immunity.
  • Single-agent ROS therapy often falls short due to adaptive antioxidant mechanisms, limiting efficacy.
  • Overexpressed ROS can paradoxically decrease the antitumor capacity of ROS-based treatments.

Purpose of the Study:

  • To design a synergistic strategy for robust ROS-based immunogenic cell death (ICD) induction.
  • To enhance ROS-mediated oxidative stress and glutathione (GSH) depletion simultaneously.
  • To develop a dual-triggered liposomal delivery system for improved cancer therapy.

Main Methods:

  • Construction of coloaded liposomes (PPA, Pyropheophorbide-alpha and SHK, shikonin) with a Fe3+ gradient.
  • Development of an acid/GSH dual triggered release profile for the liposomes.
  • Evaluation of synergistic antitumor efficacy and immune activation by depleting GSH.

Main Results:

  • The coloaded liposome (LipoPS) demonstrated acid/GSH dual triggered release.
  • Depletion of GSH by LipoPS enhanced ROS generation and amplified the ICD effect.
  • LipoPS exhibited synergistic antitumor efficacy with significant activation of antitumor immunity.

Conclusions:

  • The developed coloaded liposome LipoPS offers a promising synergistic strategy for cancer therapy.
  • LipoPS enhances ROS-mediated oxidative stress and glutathione depletion for amplified ICD.
  • This approach shows potential for further development in cancer treatment with improved therapeutic security and immune activation.