Sonosensitizer nanoplatform-mediated sonodynamic therapy induced immunogenic cell death and tumor immune
Jing Zheng1, Yixuan Sun1, Tengfei Long1
1Department of Gynecology and Obstetrics, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Abstract:
Epithelial ovarian cancer (EOC) is one of the most lethal gynecologic malignancies, and effective treatments are still lacking due to drug tolerance and tumor recurrence. In this study, we aimed to investigate the effects of sonodynamic therapy (SDT) on ovarian cancer and its potential mechanism. Folate receptor-targeted and ultrasound-responsive nanoparticles (NPs) were constructed using PLGA-PEG-FA (PLGA: poly (lactic-co-glycolic) acid, polyethylene glycol (PEG), FA: folate), the reactive oxygen species (ROS)-generating sonosensitizer IR780 and the oxygen-carrying material perfluorohexane (PFH), termed IRO@FA NPs. The antitumor effect of NPs triggered by ultrasound (US) was measured by an apoptosis assay in a C57/BL6 mouse model. Immunochemistry and flow cytometry were used to detect the proportion of CD3+ T, CD4+ T, CD8+ T cells and activated dendritic cells (DCs) in spleens and tumor tissues to assess variation in the immune response. Moreover, endoplasmic reticulum (ER) stress and immunogenic cell death (ICD) markers (high mobility group protein box-1, ATP and calreticulin) were detected to identify potential mechanisms. The results showed that IRO@FA NP-mediated SDT promoted ID8 cell apoptosis both in vitro and in vivo. The densities of CD3+ and CD8+ T lymphocytes and inflammatory markers were upregulated in tumor tissues. IRO@FA NP-mediated SDT prompted DC maturation and T lymphocyte infiltration by inducing ID8 cell ICD.
Insights
Sonodynamic therapy using targeted nanoparticles effectively triggers ovarian cancer cell death. This approach enhances anti-tumor immunity by promoting dendritic cell maturation and T cell infiltration, offering a promising new treatment strategy.
Area of Science:
- Biomedical Engineering
- Oncology
- Nanomedicine
Background:
- Epithelial ovarian cancer (EOC) presents a significant challenge due to treatment resistance and recurrence.
- Current therapies for EOC often lack efficacy, necessitating novel therapeutic strategies.
- Sonodynamic therapy (SDT) is an emerging modality with potential for targeted cancer treatment.
Purpose of the Study:
- To investigate the efficacy of folate receptor-targeted, ultrasound-responsive nanoparticles (IRO@FA NPs) in treating ovarian cancer.
- To elucidate the underlying mechanisms of SDT-induced anti-tumor effects, including immune response modulation.
- To evaluate the potential of IRO@FA NPs in combination with ultrasound for ovarian cancer therapy.
Main Methods:
- Construction of folate receptor-targeted and ultrasound-responsive nanoparticles (IRO@FA NPs) incorporating a sonosensitizer (IR780) and oxygen-carrier (PFH).
- Assessment of IRO@FA NP-mediated SDT effects on ovarian cancer cell apoptosis in vitro and in vivo using a C57/BL6 mouse model.
- Analysis of immune cell populations (CD3+, CD4+, CD8+ T cells, dendritic cells) and immunogenic cell death (ICD) markers via immunochemistry and flow cytometry.
Main Results:
- IRO@FA NP-mediated SDT significantly promoted apoptosis in ovarian cancer cells both in vitro and in vivo.
- SDT treatment led to an upregulation of CD3+ and CD8+ T lymphocytes and inflammatory markers within tumor tissues.
- IRO@FA NP-mediated SDT induced dendritic cell maturation and enhanced T lymphocyte infiltration by triggering ICD in ovarian cancer cells.
Conclusions:
- Folate receptor-targeted nanoparticles combined with ultrasound-triggered SDT demonstrate potent anti-tumor activity against epithelial ovarian cancer.
- This therapeutic approach modulates the tumor microenvironment by enhancing anti-tumor immunity through ICD induction.
- IRO@FA NP-mediated SDT represents a promising strategy for overcoming treatment resistance and recurrence in ovarian cancer.
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