Gadolinium-based ultra-small nanoparticles augment radiotherapy-induced T-cell response to synergize with checkpoint blockade immunotherapy

In the frame of radiotherapy treatment of cancer, radioresistance remains a major issue that still needs solutions to be overcome. To effectively improve the radiosensitivity of tumors and reduce the damage of radiation to neighboring normal tissues, radiosensitizers have been given increasing attention in recent years. As nanoparticles based on the metal element gadolinium, AGuIX nanoparticles have been shown to increase the radiosensitivity of cancers. Although it is a rare nanomaterial that has entered preclinical trials, the unclear biological mechanism hinders its further clinical application. In this study, we demonstrated the effectiveness of AGuIX nanoparticles in the radiosensitization of triple-negative breast cancer. We found that AGuIX nanoparticles increased the level of DNA damage by compromising the homologous recombination repair pathway instead of the non-homologous end joining pathway. Moreover, the results showed that AGuIX nanoparticles induced apoptosis, but the degree of apoptosis ability was very low, which cannot fully explain their strong radiosensitizing effect. Ferroptosis, the other mode of cell death, was also discovered to play a significant role in radiation sensitization, and AGuIX nanoparticles may regulate the anti-ferroptosis system by inhibiting the NRF2-GSH-GPX4 signaling pathway. Graphical Abstract

show abstract

“…The synthesis and material characterization of the AGuIX nanoparticles was performed as previously described [ 16 , 50 , 51 ].…”

Section: Methodsmentioning

confidence: 99%

AGuIX nanoparticles enhance ionizing radiation-induced ferroptosis on tumor cells by targeting the NRF2-GPX4 signaling pathway

Sun

Cai

et al. 2022

J Nanobiotechnol

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Nanomedicines Aid In Cancer Radio-immunotherapymentioning

confidence: 99%

“…For example, in one aspect, nanoradiosensitizers augment local radiation deposition and improve radioresistance, resulting in increased ICD and in situ vaccination. 38,39 In other aspects, nanocarriers with/without intrinsic bioactive properties have been applied to deliver therapeutic/ diagnostic radionuclides, tumor antigens, ICIs, and immunomodulators to provoke strong, durable antitumor immunity, address immunosuppression, and realize imaging-aided therapy. 40,41 Besides, incorporation of nanomedicines into adoptive cells or CAR T cells to deliver ICIs represents a clinical translational path for radio-immunotherapy.…”

Section: Hu Zhangmentioning

confidence: 99%

“…NBTXR3 (phase III, status: recruiting) and AGuIX (phase II, status: recruiting) are two examples of inorganic nano-radiosensitizers. 39 In preclinical studies, a great sum of inorganic nanomedicines, such as aluminum NPs, CaCO 3 NPs, metal oxide NPs (e.g., MnO 2 ), and mesoporous silica NPs, emerge as potent radiosensitizers, immuno-adjuvants or carriers. These inorganic nanomedicines exhibit high Z metal-or hypoxia relief-mediated radiation sensitization, display inherent or acquired immunomodulatory effects, and possess a high drug-loading capacity.…”

Section: Design Strategies Of Nanomedicines For Radioimmunotherapymentioning

confidence: 99%

See 1 more Smart Citation

Nanomedicine embraces cancer radio-immunotherapy: mechanism, design, recent advances, and clinical translation

Luo

Zhang

et al. 2023

Chem. Soc. Rev.

View full text Add to dashboard Cite

show abstract

“…discovered that AGuIX could intensify the RT‐induced ICD of B16 cancer cells to expose CRT and secrete HMGB1, which in combination with PD1 blockade therapy would stimulate remarkable immune response against bilateral tumors and metastasis ( Figure A). [ 85 ]…”

Section: Enhancement Of Rt For Icdmentioning

confidence: 99%

Radiation‐Induced Immunogenic Cell Death for Cancer Radioimmunotherapy

Pei

Shen

et al. 2023

Small Methods

View full text Add to dashboard Cite

In cancer treatment, traditional radiotherapy (RT) is routinely conducted in local tumors and limited by radioresistance, while recently emerged immunotherapy is confronted with low response rate, high cost, and cytokine release syndrome. Logically, the combination of the two therapeutic modalities into radioimmunotherapy is promising to complement with each other for systemic elimination of cancer cells with high specificity, efficiency, and safety. Especially, RT‐induced immunogenic cell death (ICD) plays an imperative role in radioimmunotherapy to evoke systemic immune response against cancer, including elevating the immunity of tumor antigens, recruiting and activating antigen‐presenting cells, and priming cytotoxic T lymphocytes for tumoral infiltration and cancer cell eradication. This review first retrospects the origin and concept of ICD, summarizes the major damage‐associated molecular patterns and signaling pathways, and highlights the characteristics of RT‐induced ICD. Subsequently, therapeutic strategies enhancing RT‐induced ICD for radioimmunotherapy are reviewed from the perspectives of enhancing RT itself, combination with other treatments, and stimulating the holistic immune system. On the basis of these published research and underlying mechanism, this work attempts to forecast possible directions for RT‐induced ICD enhancement to promote clinical applications.

show abstract

Gadolinium-based ultra-small nanoparticles augment radiotherapy-induced T-cell response to synergize with checkpoint blockade immunotherapy

Abstract: Radiotherapy suffers from its high-dose radiation-induced systemic toxicity and radioresistance caused by the immunosuppressive tumor microenvironment. Immunotherapy using checkpoint blocking in solid tumors shows limited anticancer efficacy due to insufficient...

Cited by 17 publications

References 59 publications

AGuIX nanoparticles enhance ionizing radiation-induced ferroptosis on tumor cells by targeting the NRF2-GPX4 signaling pathway

AGuIX nanoparticles enhance ionizing radiation-induced ferroptosis on tumor cells by targeting the NRF2-GPX4 signaling pathway

Nanomedicine embraces cancer radio-immunotherapy: mechanism, design, recent advances, and clinical translation

Radiation‐Induced Immunogenic Cell Death for Cancer Radioimmunotherapy

Contact Info

Product

Resources

About