黏附蛋白偶联热响应性杂化纳米粒子用于光热和免疫治疗癌症及其转移。
adhesin protein-conjugated thermal responsive hybrid nanoparticles for photothermal and immunotherapy against cancer and its metastasis.
机构信息
Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Medical Biotechnology, Yeungnam University, Gyeongsan, Republic of Korea.
出版信息
J Immunother Cancer. 2021 Jul;9(7). doi: 10.1136/jitc-2021-002666.
BACKGROUND
Advanced cancer therapy is targeted at primary tumors and also recurrent or metastatic cancers. Combinational cancer treatment has recently shown high efficiency against recurrent and metastatic cancers. In this study, we synthesized a thermal responsive hybrid nanoparticle (TRH) containing FimH, an immune stimulatory recombinant protein, for the induction of a combination of photothermal therapy (PTT) and immunotherapy against cancer and its metastasis.
METHODS
The hybrid nanoparticle was incorporated with a near-infrared (NIR) absorbent, indocyanine green, and decorated with FimH on its surface to form F-TRH. F-TRH was evaluated for its anticancer and antimetastatic effects against CT-26 carcinoma in mice by combining PTT and immunotherapy.
RESULTS
NIR laser irradiation elicited an elevation of temperature in F-TRH, which induced apoptosis in CT-26 carcinoma cells in vitro. In addition, F-TRH and NIR laser irradiation promoted photothermal-mediated therapeutic effects against CT-26 and 4T1 tumors in mice. The release of FimH from F-TRH in response to elevated temperature and apoptotic bodies of cancer cells via PTT elicited dendritic cell-mediated cancer antigen-specific T-cell responses, which subsequently inhibited the second challenge of CT-26 and 4T1 cell growth in the lung.
CONCLUSIONS
These data demonstrate the potential use of F-TRH for immuno-photothermal therapy against cancer and its recurrence and metastasis.
背景
先进的癌症疗法针对的是原发性肿瘤以及复发性或转移性癌症。联合癌症治疗最近对复发性和转移性癌症显示出了很高的效率。在这项研究中，我们合成了一种包含 FimH 的热响应性杂化纳米颗粒（TRH），用于诱导光热疗法（PTT）和免疫疗法相结合来治疗癌症及其转移。
方法
杂化纳米颗粒与近红外（NIR）吸收剂吲哚菁绿结合，并在其表面装饰 FimH 以形成 F-TRH。通过结合 PTT 和免疫疗法，用 F-TRH 评估其对 CT-26 癌小鼠的抗癌和抗转移作用。
结果
NIR 激光照射引起 F-TRH 温度升高，导致体外 CT-26 癌细胞凋亡。此外，F-TRH 和 NIR 激光照射促进了 F-TRH 和 NIR 激光照射对小鼠 CT-26 和 4T1 肿瘤的光热介导治疗作用。FimH 从 F-TRH 中的释放响应于升高的温度和癌细胞的凋亡体通过 PTT 引发树突状细胞介导的癌症抗原特异性 T 细胞反应，随后抑制 CT-26 和 4T1 细胞在肺部的第二次生长。
结论
这些数据表明 F-TRH 具有用于免疫光热治疗癌症及其复发和转移的潜力。
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