Nanosonosensitizers With Ultrasound-Induced Reactive Oxygen Species Generation for Cancer Sonodynamic Immunotherapy

Cheng, Danling; Wang, Xiaoying; Zhou, Xiaojun; Li, Jingchao

doi:10.3389/fbioe.2021.761218

Cited by 21 publications

(15 citation statements)

References 55 publications

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“…Calreticulin (CRT) exposure on the cell membrane and damage‐related molecular patterns (DAMPs) secreted from the cell, including high mobility group box 1 (HMGB1), are considered as commonly used detection factors for ICD. [ 23 ] The CRT exposure on the surface of B16‐F10 cells was assessed by immunofluorescence confocal microscopy. The results revealed that Ru‐TePt@siRNA‐MVs + US group induced higher levels of CRT exposure on the cell surface than the untreated group (Figure S17, Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

Integrated Nanorod‐Mediated PD‐L1 Downregulation in Combination with Oxidative‐Stress Immunogene Therapy against Cancer

Zhang

Pan

et al. 2023

Adv Healthcare Materials

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It is an engaging program for tumor treatment that rationalizes the specific microenvironments, activation of suppressed immune system (immune resistance/escape reversion), and synergistic target therapy. Herein, a biomimetic nanoplatform that combines oxidative stress with genetic immunotherapy to strengthen the therapeutic efficacy is developed. Ru‐TePt nanorods, small interfering RNA (PD‐L1 siRNA), and biomimetic cellular membrane vesicles with the targeting ability to design a multifunctional Ru‐TePt@siRNA‐MVs system are rationally integrated. Notably, the Fenton‐like activity significantly enhances Ru‐TePt nanorods sonosensitization, thus provoking stronger oxidative stress to kill cells directly. Meanwhile, immunogenic cell death is triggered to secrete numerous cytokines and activate T cells. The effective catalase characteristics of Ru‐TePt enable the in situ oxygen‐producing pump to improve tumor oxygen level and coordinately strengthen the therapeutic effect of SDT followed. More importantly, anti‐PD‐L1‐siRNA mediated immune checkpoint silence of the PD‐L1 gene creates an environment conducive to activating cytotoxic T lymphocytes, synergistic with boosted reactive oxygen species‐triggered antitumor immune response. The experimental results in vitro and in vivo reveal that the Ru‐TePt@siRNA‐MVs nanosystems can effectively activate the oxidative stress‐triggered immune response and inhibit PD‐1/PD‐L1 axis‐mediated immune resistance. Consequently, this orchestrated treatment paradigm provides valuable insights for developing potential oxidative stress and genetic immunotherapy.

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Section: Resultsmentioning

confidence: 99%

Integrated Nanorod‐Mediated PD‐L1 Downregulation in Combination with Oxidative‐Stress Immunogene Therapy against Cancer

Zhang

Pan

et al. 2023

Adv Healthcare Materials

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“…Owing to SDT can generate intracellular ROS to induce ICD, immunofluorescence staining of CRT in MC38 cells, a common ICD marker that could stimulate antigen presentation and induce immune response ( 19 , 20 ) was conducted. As shown in Figure 3D and Supplementary Figure 2C , cells treated with nanodrugs alone or US irradiation alone exhibited negligible green fluorescence.…”

Section: Resultsmentioning

confidence: 99%

Perfluorocarbon nanodrug induced oxygen self-enriching sonodynamic therapy improves cancer immunotherapy after insufficient radiofrequency ablation

Huang

et al. 2023

Front. Immunol.

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Residual lesions and undetectable metastasis after insufficient radiofrequency ablation (iRFA) are associated with earlier new metastases and poor survival in cancer patients, for induced aggressive tumor phenotype and immunosuppression. Programmed cell death protein 1(PD-1) blockade has been reported to enhance the radiofrequency ablation-elicited antitumor immunity, but its ability to eliminate incompletely ablated residual lesions has been questioned. Here, we report a combined treatment modality post iRFA based on integrating an oxygen self-enriching nanodrug PFH-Ce6 liposome@O2 nanodroplets (PCL@O2)-augmented noninvasive sonodynamic therapy (SDT) with PD-1 blockade. PCL@O2 containing Ce6 as the sonosensitizer and PFH as O2 reservoir, was synthesized as an augmented SDT nanoplatform and showed increased ROS generation to raise effective apoptosis of tumor cells, which also exposed more calreticulin to induce stronger immunogenic cell death (ICD). Combining with PD-1 blockade post iRFA, this optimized SDT induced a better anti-tumor response in MC38 tumor bearing mouse model, which not only arrested residual primary tumor progression, but also inhibited the growth of distant tumor, therefore prolonging the survival. Profiling of immune populations within the tumor draining lymph nodes and tumors further revealed that combination therapy effectively induced ICD, and promoted the maturation of dendritic cells, tumor infiltration of T cells, as well as activation of cytotoxic T lymphocytes. While iRFA alone could result in an increase of regulatory T cells (Tregs) in the residual tumors, SDT plus PD-1 blockade post iRFA reduced the number of Tregs in both primary and distant tumors. Moreover, the combined treatment could significantly initiate long-term immune memory, manifesting as elevated levels of CD8+ and CD4+ central memory cells. Therefore, this study establishes the preclinical proof of concept to apply oxygen self-enriching SDT to augment cancer immunotherapy after iRFA.

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“…Moreover, some emerging ablation technologies are also exploring the possibility of combining with immunotherapy. For example, after photodynamic therapy, various immune cells, including T cells, DCs, neutrophils, NK cells and macrophages are activated, Treg cells are increased and PD-L1 expression is up-regulated ( 46 ).At the same time, sonodynamic therapy can trigger systemic immune responses by eliciting ICD and repolarize macrophages from immunosuppressive M2 to antitumor M1 phenotypes ( 60 ). Which indicates that the combination of dynamic therapy and immunotherapy is a good strategy.…”

Section: Discussionmentioning

confidence: 99%

Knowledge mapping of image-guided tumor ablation and immunity: A bibliometric analysis

et al. 2023

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BackgroundVarious ablation techniques have been successfully applied in tumor therapy by locally destroying tumor. In the process of tumor ablation, a large number of tumor cell debris is released, which can be used as a source of tumor antigens and trigger a series of immune responses. With the deepening of the research on the immune microenvironment and immunotherapy, researches exploring tumor ablation and immunity are continuously published. However, no research has systematically analyzed the intellectual landscape and emerging trends for tumor ablation and immunity using scientometric analysis. Therefore, this study aimed to conduct a bibliometric analysis to quantify and identify the status quo and trend of tumor ablation and immunity.MethodsData of publications were downloaded from the Web of Science Core Collection database. CiteSpace and VOSviewer were used to conduct bibliometric analysis to evaluate the contribution and co-occurrence relationship of different countries/regions, institutions and authors in the field, and to determine the research hotspots in this field.ResultsBy searching in the database, a total of 3531 English articles published between 2012 and 2021 were obtained. We observed rapid growth in the number of publications since 2012. The two most active countries were China and the United States, with more than 1,000 articles. Chinese Academy of Sciences contributed the most publications (n = 153). Jibing Chen and Xianzheng Zhang might have a keen interest in tumor ablation and immunity, with more publications (n = 14; n = 13). Among the top 10 co-cited authors, Castano AP (284 citations) was ranked first, followed by Agostinis P (270 citations) and Chen Qian (246 citations). According to the co-occurrence and cluster analysis, the results indicated that the focus of research was “photothermal therapy” and “immune checkpoint blockade”.ConclusionsIn the past decade, the neighborhood of tumor ablation domain immunity has been paid more and more attention. Nowadays, the research hotspots in this field are mainly focused on exploring the immunological mechanism in photothermal therapy to improve its efficacy, and the combination of ablation therapy and immune checkpoint inhibitor therapy.

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Nanosonosensitizers With Ultrasound-Induced Reactive Oxygen Species Generation for Cancer Sonodynamic Immunotherapy

Cited by 21 publications

References 55 publications

Integrated Nanorod‐Mediated PD‐L1 Downregulation in Combination with Oxidative‐Stress Immunogene Therapy against Cancer

Integrated Nanorod‐Mediated PD‐L1 Downregulation in Combination with Oxidative‐Stress Immunogene Therapy against Cancer

Perfluorocarbon nanodrug induced oxygen self-enriching sonodynamic therapy improves cancer immunotherapy after insufficient radiofrequency ablation

Knowledge mapping of image-guided tumor ablation and immunity: A bibliometric analysis

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