Yang Jingxing, Hou Mengfei, Sun Wenshe, Wu Qinghe, Xu Jia, Xiong Liqin, Chai Yimin, Liu Yuxin, Yu Meihua, Wang Haolu, Xu Zhi Ping, Liang Xiaowen, Zhang Chunfu
Department of Orthopedics Shanghai Jiao Tong University Affiliated 6th Hospital School of Biomedical Engineering Shanghai Jiao Tong University Shanghai 200030 China.
Department of Nuclear Medicine Rui Jin Hospital School of Biomedical Engineering Shanghai Jiao Tong University Shanghai 200030 China.
Adv Sci (Weinh). 2020 Jul 1;7(16):2001088. doi: 10.1002/advs.202001088. eCollection 2020 Aug.
Immune responses stimulated by photodynamic therapy (PDT) and photothermal therapy (PTT) are a promising strategy for the treatment of advanced cancer. However, the antitumor efficacy by PDT or PTT alone is less potent and unsustainable against cancer metastasis and relapse. In this study, Gd and chlorin e6 loaded single-walled carbon nanohorns (Gd-Ce6@SWNHs) are developed, and it is demonstrated that they are a strong immune adjuvant, and have high tumor targeting and penetration efficiency. Then, three in vivo mouse cancer models are established, and it is found that sequential PDT and PTT using Gd-Ce6@SWNHs synergistically promotes systemic antitumor immune responses, where PTT stimulates dendritic cells (DCs) to secrete IL-6 and TNF-, while PDT triggers upregulation of IFN- and CD80. Moreover, migration of Gd-Ce6@SWNHs from the targeted tumors to tumor-draining lymph nodes sustainably activates the DCs to generate a durable immune response, which eventually eliminates the distant metastases without using additional therapeutics. Gd-Ce6@SWNHs intervened phototherapies also generate durable and long-term memory immune responses to tolerate and prevent cancer rechallenge. Therefore, this study demonstrates that sequential PDT and PTT using Gd-Ce6@SWNHs under moderate conditions elicits cooperative and long-lasting antitumor immune responses, which are promising for the treatment of patients with advanced metastatic cancers.
光动力疗法（PDT）和光热疗法（PTT）刺激产生的免疫反应是治疗晚期癌症的一种很有前景的策略。然而，单独使用PDT或PTT的抗肿瘤疗效在对抗癌症转移和复发方面较弱且不可持续。在本研究中，制备了负载钆（Gd）和二氢卟吩e6（Ce6）的单壁碳纳米角（Gd-Ce6@SWNHs），并证明它们是一种强大的免疫佐剂，具有高肿瘤靶向性和渗透效率。然后，建立了三种体内小鼠癌症模型，发现使用Gd-Ce6@SWNHs依次进行PDT和PTT可协同促进全身抗肿瘤免疫反应，其中PTT刺激树突状细胞（DCs）分泌白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α），而PDT触发干扰素-γ（IFN-γ）和CD80的上调。此外，Gd-Ce6@SWNHs从靶向肿瘤迁移至肿瘤引流淋巴结可持续激活DCs以产生持久的免疫反应，最终无需使用额外的治疗方法即可消除远处转移灶。Gd-Ce6@SWNHs干预的光疗法还产生持久的长期记忆免疫反应，以耐受和预防癌症再次攻击。因此，本研究表明，在适度条件下使用Gd-Ce6@SWNHs依次进行PDT和PTT可引发协同且持久的抗肿瘤免疫反应，这对于治疗晚期转移性癌症患者很有前景。
