Yu Hao, Liu Wenjing, Ding Kaikai, Wu Jiangjie, Wang Cheng, Wang Siyuan, Wu Lingyun, Tang Qiuying, Yin Xin, Jiang Kan, Yan Danfang, Wang Xu, Chen Si, Yan Senxiang
Department of Radiation Oncology, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, Zhejiang, 310003, P. R. China.
College of Materials Science and Engineering, Zhejiang Key Laboratory of Plastic Modification and Processing Technology, Zhejiang University of Technology, Hangzhou, 310014, P. R. China.
Adv Sci (Weinh). 2025 Feb;12(5):e2408323. doi: 10.1002/advs.202408323. Epub 2024 Dec 11.
Glioblastoma (GBM) remains a daunting oncological challenge because of its aggressive nature and resistance to conventional therapies. Inhibition of the intrinsic STING pathway in GBM hampers the effectiveness of immunotherapies. To overcome this clinical limitation, a Sequential Release HydroLipo System (SRHLS) is developed, in which hydrogels and nanoparticles are combined for controlled drug release. The SRHLS sequentially released decitabine and STING agonists, thereby correcting STING signaling dysfunction through epigenetic reprogramming and enhancing antitumor immunity. According to in vitro and in vivo experiments, the SRHLS reshaped the tumor microenvironment and markedly inhibited tumor growth, recurrence, and metastasis. These findings underscore the potential of the SRHLS as a promising therapeutic strategy for GBM.
胶质母细胞瘤（GBM）因其侵袭性和对传统疗法的耐药性，仍然是一个严峻的肿瘤学挑战。抑制GBM中固有的STING通路会阻碍免疫疗法的有效性。为了克服这一临床局限性，开发了一种顺序释放水脂系统（SRHLS），其中水凝胶和纳米颗粒相结合以实现药物的可控释放。SRHLS顺序释放地西他滨和STING激动剂，从而通过表观遗传重编程纠正STING信号功能障碍并增强抗肿瘤免疫力。根据体外和体内实验，SRHLS重塑了肿瘤微环境，并显著抑制了肿瘤的生长、复发和转移。这些发现强调了SRHLS作为一种有前景的GBM治疗策略的潜力。
