Cai Songhua, Huang Jing, Fan Hongjie, Sui Zhilin, Huang Chujian, Deng Youjun, Jia Ran, Wang Lixu, Ma Kai, Guo Xiaotong, He Jie, Zhang Baihua, Yu Zhentao
Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, China.
Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Nanobiotechnology. 2025 Jun 2;23(1):409. doi: 10.1186/s12951-025-03428-5.
Lung adenocarcinoma (LUAD) is a refractory tumor with high incidence, high mortality, and easy development of drug resistance. Represented by PD-L1, the rise of immunotherapy and multidrug combinations offers a reliable approach to treating LUAD. However, there are still some patients with immunoresistance or insensitivity, and new combination therapies are still needed.
In this study, cyclic arginine-glycine-aspartate (cRGD)/erythrocyte membrane (RBCM) double-head nanocarriers were designed. This nanocarrier platform targets CTRP6 in tumors and delivers gemcitabine to block the progression of lung cancer. PD-L1 monoclonal antibodies were used as a codelivery platform to explore the effect of the codelivery platform on immunotherapy.
CTRP6 expression was negatively correlated with the prognosis of patients with lung adenocarcinoma. The codelivery platform @RBCM/cRGD-PhLips effectively targeted tumor cells. Co-carrying gemcitabine and targeting CTRP6 expression, it amplified ferroptosis of tumor cells through the NRF2/STAT3 signaling pathway, activated intratumoral immunity, and promoted M1-like macrophage transformation and CD8 T-cell recruitment. This platform amplified the immune effect of PD-L1 monoclonal antibodies to play an anti-lung cancer role.
The synergistic delivery of the targeted tumor cell-intrinsic CTRP6 biomimetic nanocarrier provides a new approach to the combined immunotherapy of lung cancer.
肺腺癌（LUAD）是一种难治性肿瘤，具有高发病率、高死亡率且易产生耐药性。以程序性死亡受体配体1（PD-L1）为代表，免疫疗法和多药联合的兴起为治疗肺腺癌提供了一种可靠的方法。然而，仍有一些患者存在免疫抵抗或不敏感情况，仍需要新的联合治疗方法。
在本研究中，设计了环状精氨酸-甘氨酸-天冬氨酸（cRGD）/红细胞膜（RBCM）双头纳米载体。该纳米载体平台靶向肿瘤中的卷曲霉素相关蛋白6（CTRP6），并递送吉西他滨以阻断肺癌进展。使用PD-L1单克隆抗体作为共递送平台，以探究该共递送平台对免疫治疗的效果。
CTRP6表达与肺腺癌患者的预后呈负相关。共递送平台@RBCM/cRGD-PhLips有效靶向肿瘤细胞。共携带吉西他滨并靶向CTRP6表达，它通过核因子E2相关因子2（NRF2）/信号转导和转录激活因子3（STAT3）信号通路放大肿瘤细胞的铁死亡，激活肿瘤内免疫，并促进M1型巨噬细胞转化和CD8 T细胞募集。该平台放大了PD-L1单克隆抗体的免疫效果，发挥抗肺癌作用。
靶向肿瘤细胞内源性CTRP6的仿生纳米载体的协同递送为肺癌联合免疫治疗提供了一种新方法。
