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Bioactive Nanoliposomes for Enhanced Sonodynamic-Triggered Disulfidptosis-Like Cancer Cell Death via Lipid
Hongwei Xiang1, Bin Shen1, Chunmei Zhang1
1Department of Ultrasound, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Introduction:
Cell death regulation holds a unique value in the field of cancer therapy. Recently, disulfidptosis has garnered substantial scientific attention. Previous studies have reported that sonodynamic therapy (SDT) based on reactive oxygen species (ROS) can regulate cancer cell death, achieving an limited anti-cancer effect. However, the integration of SDT with disulfidptosis as an anti-cancer strategy has not been extensively developed. In this study, we constructed an artificial membrane disulfidptosis sonosensitizer, specifically, a nanoliposome (SC@lip) coated with a combination of the chemotherapy medicine Sorafenib (Sora) and sonosensitizer Chlorin e6 (Ce6), to realize a one-stop enhanced SDT effect that induces disulfidptosis-like cancer cell death.
Methods:
Sorafenib and Ce6 were co-encapsulated into PEG-modified liposomes, and SC@Lip was constructed using a simple rotary evaporation phacoemulsification method. The cell phagocytosis, ROS generation ability, glutathione (GSH) depletion ability, lipid peroxidation (LPO), and disulfidptosis-like death mediated by SC@Lip under ultrasound (US) irradiation were evaluated. Based on a 4T1 subcutaneous tumor model, both the in vivo biological safety assessment and the efficacy of SDT were assessed.
Results:
SC@Lip exhibits high efficiency in cellular phagocytosis. After being endocytosed by 4T1 cells, abundant ROS were produced under SDT activation, and the cell survival rates were below 5%. When applied to a 4T1 subcutaneous tumor model, the enhanced SDT mediated by SC@Lip inhibited tumor growth and prolonged the survival time of mice. In vitro and in vivo experiments show that SC@Lip can enhance the SDT effect and trigger disulfidptosis-like cancer cell death, thus achieving anti-tumor efficacy both in vitro and in vivo.
Conclusion:
SC@Lip is a multifunctional nanoplatform with an artificial membrane, which can integrate the functions of sonosensitization and GSH depletion into a biocompatible nanoplatform, and can be used to enhance the SDT effect and promote disulfidptosis-like cancer cell death.
Insights
This study introduces SC@Lip, a nanoplatform that combines sonodynamic therapy (SDT) with disulfidptosis to enhance cancer cell death. The novel approach shows significant anti-tumor efficacy in preclinical models by inducing targeted cell death.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Cell death regulation is crucial for cancer therapy.
- Sonodynamic therapy (SDT) uses reactive oxygen species (ROS) for cancer treatment but has limitations.
- Disulfidptosis is an emerging cell death pathway of interest in oncology.
Purpose of the Study:
- To develop an enhanced sonodynamic therapy (SDT) strategy by integrating it with disulfidptosis.
- To construct a novel nanoplatform, SC@Lip, for targeted cancer cell death induction.
- To evaluate the anti-tumor efficacy of the SC@Lip nanoplatform in vitro and in vivo.
Main Methods:
- SC@Lip nanoliposomes were fabricated by co-encapsulating Sorafenib (Sora) and Chlorin e6 (Ce6).
- Evaluated cellular uptake, ROS generation, glutathione (GSH) depletion, and lipid peroxidation (LPO) in 4T1 cells.
- Assessed in vivo biological safety and anti-tumor efficacy using a 4T1 subcutaneous tumor model under ultrasound (US) irradiation.
Main Results:
- SC@Lip demonstrated high cellular phagocytosis and significant ROS production upon SDT activation.
- SC@Lip treatment resulted in <5% cell survival rates in 4T1 cells.
- In vivo studies showed SC@Lip inhibited tumor growth and prolonged survival in mice, with no significant toxicity.
Conclusions:
- SC@Lip is a multifunctional nanoplatform integrating sonosensitization and GSH depletion.
- This platform effectively enhances SDT and promotes disulfidptosis-like cancer cell death.
- SC@Lip offers a promising strategy for improved anti-tumor efficacy.
