PDF(Pubmed)
Abstract：
BACKGROUND: Triple-negative breast cancer (TNBC) was closely related to high metastatic risk and mortality and has not yet found a targeted receptor for targeted therapy. Cancer immunotherapy, especially photoimmunotherapy, shows promising potential in TNBC treatment because of great spatiotemporal controllability and non-trauma. However, the therapeutic effectiveness was limited by insufficient tumor antigen generation and the immunosuppressive microenvironment.
METHODS: We report on the design of cerium oxide (CeO2) end-deposited gold nanorods (CEG) to achieve excellent near-infrared photoimmunotherapy. CEG was synthesized through hydrolyzing of ceria precursor (cerium acetate, Ce(AC)3) on the surface of Au nanorods (NRs) for cancer therapy. The therapeutic response was first verified in murine mammary carcinoma (4T1) cells and then monitored by analysis of the anti-tumor effect in xenograft mouse models.
RESULTS: Under near-infrared (NIR) light irradiation, CEG can efficiently generate hot electrons and avoid hot-electron recombination to release heat and form reactive oxygen species (ROS), triggering immunogenic cell death (ICD) and activating part of the immune response. Simultaneously, combining with PD-1 antibody could further enhance cytotoxic T lymphocyte infiltration.
CONCLUSIONS: Compared with CBG NRs, CEG NRs showed strong photothermal and photodynamic effects to destroy tumors and activate a part of the immune response. Combining with PD-1 antibody could reverse the immunosuppressive microenvironment and thoroughly activate the immune response. This platform demonstrates the superiority of combination therapy of photoimmunotherapy and PD-1 blockade in TNBC therapy.
METHODS: We report on the design of cerium oxide (CeO2) end-deposited gold nanorods (CEG) to achieve excellent near-infrared photoimmunotherapy. CEG was synthesized through hydrolyzing of ceria precursor (cerium acetate, Ce(AC)3) on the surface of Au nanorods (NRs) for cancer therapy. The therapeutic response was first verified in murine mammary carcinoma (4T1) cells and then monitored by analysis of the anti-tumor effect in xenograft mouse models.
RESULTS: Under near-infrared (NIR) light irradiation, CEG can efficiently generate hot electrons and avoid hot-electron recombination to release heat and form reactive oxygen species (ROS), triggering immunogenic cell death (ICD) and activating part of the immune response. Simultaneously, combining with PD-1 antibody could further enhance cytotoxic T lymphocyte infiltration.
CONCLUSIONS: Compared with CBG NRs, CEG NRs showed strong photothermal and photodynamic effects to destroy tumors and activate a part of the immune response. Combining with PD-1 antibody could reverse the immunosuppressive microenvironment and thoroughly activate the immune response. This platform demonstrates the superiority of combination therapy of photoimmunotherapy and PD-1 blockade in TNBC therapy.
摘要：
背景：三阴性乳腺癌（TNBC）与高转移风险和死亡率密切相关，尚未找到靶向治疗的靶向受体。癌症免疫疗法,尤其是光免疫疗法，由于巨大的时空可控性和非创伤性，在TNBC治疗中显示出有希望的潜力。然而,治疗效果受到肿瘤抗原产生不足和免疫抑制微环境的限制.
方法：我们报告了氧化铈（CeO2）末端沉积的金纳米棒（CEG）的设计，以实现出色的近红外光免疫疗法。CEG是通过水解二氧化铈前体(乙酸铈，Au纳米棒（NRs）表面的Ce（AC）3）用于癌症治疗。首先在鼠乳腺癌（4T1）细胞中验证治疗反应，然后通过分析异种移植小鼠模型中的抗肿瘤作用来监测。
结果：在近红外（NIR）光照射下，CEG可以有效地产生热电子并避免热电子复合以释放热量并形成活性氧（ROS），触发免疫原性细胞死亡（ICD）并激活部分免疫反应。同时,结合PD-1抗体可进一步增强细胞毒性T淋巴细胞浸润。
结论：与CBGNR相比，CEGNRs表现出强烈的光热和光动力效应以破坏肿瘤并激活一部分免疫应答。结合PD-1抗体可以逆转免疫抑制微环境，彻底激活免疫反应。该平台证明了光免疫疗法和PD-1阻断联合治疗在TNBC治疗中的优越性。
方法：我们报告了氧化铈（CeO2）末端沉积的金纳米棒（CEG）的设计，以实现出色的近红外光免疫疗法。CEG是通过水解二氧化铈前体(乙酸铈，Au纳米棒（NRs）表面的Ce（AC）3）用于癌症治疗。首先在鼠乳腺癌（4T1）细胞中验证治疗反应，然后通过分析异种移植小鼠模型中的抗肿瘤作用来监测。
结果：在近红外（NIR）光照射下，CEG可以有效地产生热电子并避免热电子复合以释放热量并形成活性氧（ROS），触发免疫原性细胞死亡（ICD）并激活部分免疫反应。同时,结合PD-1抗体可进一步增强细胞毒性T淋巴细胞浸润。
结论：与CBGNR相比，CEGNRs表现出强烈的光热和光动力效应以破坏肿瘤并激活一部分免疫应答。结合PD-1抗体可以逆转免疫抑制微环境，彻底激活免疫反应。该平台证明了光免疫疗法和PD-1阻断联合治疗在TNBC治疗中的优越性。
