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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.
Abstract:
Reactive oxygen species (ROS) can not only induce cellular oxidative stress, but also trigger antitumor immune response. However, single ROS generated therapy is usually not enough to induce efficient antitumor immune response. Furthermore, the adaptive antioxidant mechanisms coupled with overexpressed ROS can also decrease the antitumor capacity of ROS therapy. To circumvent this problem, we designed a synergistic strategy for inducing robust ROS based ICD effect by constructing a coloaded liposomes (PPA, Pyropheophorbide-alpha and SHK, shikonin) with Fe3+ gradient to simultaneously enhance ROS mediated oxidative stress and glutathione depletion. Interestingly, the coloaded liposome possesses an acid/GSH dual triggered release profile. More importantly, with the help of depleting GSH, LipoPS (coloaded liposome of SHK and PPA) can excite robust ROS and demonstrate synergistic antitumor efficacy with amplified ICD effect. Summarized, the established coloaded liposome LipoPS exhibits good therapeutic security and synergistic antitumor effect with strong antitumor immune activation, providing potential for further development.
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.
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