Phase-Transformation Nanoparticle-Mediated Sonodynamic Therapy: An Effective Modality to Enhance Anti-Tumor Immune Response by Inducing Immunogenic Cell Death in Breast Cancer

Abstract

Purpose Immunologically quiescent of breast cancer cells has been recognized as the key impediment for the breast cancer immunotherapy. In this study, we aimed to investigate the role of nanoparticle-mediated sonodynamic therapy (SDT) in promoting anti-tumor immune of breast cancer cells and its potential immune mechanisms. Materials and Methods The phase-transformation nanoparticles (LIP-PFH nanoparticles) were in-house prepared and its physiochemical characters were detected. The CCK-8 assay, apoptosis analysis and Balb/c tumor model establishment were used to explore the anti-tumor effect of LIP-PFH nanoparticles triggered by low-intensity focused ultrasound (LIFU) both in vitro and in vivo. Flow cytometry and immunohistochemistry of CD4 + T, CD8 + T, CD8 + PD-1 + T in blood, spleen and tumor tissue were performed to represent the change of immune response. Detection of immunogenic cell death (ICD) markers was examined to study the potential mechanisms. Results LIP-PFH nanoparticles triggered by LIFU could inhibit the proliferation and promote the apoptosis of 4T1 cells both in vitro and in vivo. CD4 + T and CD8 + T cell subsets were significantly increased in blood, spleen and tumor tissue, meanwhile CD8 + PD-1 + T cells were reduced, indicating enhancement of anti-tumor immune response of breast cancer cells in the nanoparticle-mediated SDT group. Detection of ICD markers (ATP, high-mobility group box B1, and calreticulin) and flow cytometric analysis of dendritic cell (DC) maturity further showed that the nanoparticle-mediated SDT can promote DC maturation to increase the proportion of cytotoxic T cells by inducing ICD of breast cancer cells. Conclusion The therapy of nanoparticles-mediated SDT can effectively enhance anti-tumor immune response of breast cancer.

Sonosensitizer nanoplatform-mediated sonodynamic therapy induced immunogenic cell death and tumor immune microenvironment variation

“…Photothermal therapy and sonodynamic therapy have been demonstrated to boost lymphocyte infiltration and augment the antitumor effects of ICIs (Liang et al., 2019 ; Zhang et al., 2020 ; Si et al., 2021 ) reported that pure oxygen-carrying NPs triggered by US also have the ability to activate antitumor immunity in the body. Combining nanomedicine with immunotherapy is an important method to improve therapeutic effects (Ye et al., 2019 ; Lin et al., 2021 ).…”

Ultrasound Molecular Imaging and Its Applications in Cancer Diagnosis and Therapy

“…52 Si et al used phase-transformation nanoparticles to demonstrate that nanoparticle-mediated sonodynamic therapy can effectively enhance the antitumor immune response of breast cancer. 53 With the increasing demand for precise and personalized therapeutic treatments, a large number of sonosensitizers with imaging capabilities have been investigated for significantly enhancing treatment efficacy.…”

Application of nanosonosensitizer materials in cancer sono-dynamic therapy

“…The results showed that nanoparticle-mediated SDT could promote DC maturation by inducing ICD in breast cancer cells to increase the proportion of cytotoxic T cells. 57 Macrophages have a wide range of biological functions and are essential cells involved in innate immunity and adaptive immunity. 58 Ji et al developed mitochondria-targeted and ultrasound-responsive nanoparticles to co-deliver oxygen (O 2 ) and nitric oxide (NO) to enhance SDT and immune responses.…”