免疫原性细胞死亡
内质网
氯霉素
未折叠蛋白反应
阿霉素
细胞毒性
结合
光热治疗
细胞生物学
癌症研究
生物物理学
材料科学
化学
体外
生物化学
生物
纳米技术
细胞凋亡
化疗
程序性细胞死亡
数学分析
环磷酰胺
遗传学
数学
作者
Minjie Zhang,Xin Jin,Meng Gao,Yunjiao Zhang,Ben Zhong Tang
标识
DOI:10.1002/adma.202205701
摘要
Immunogenic cell death (ICD) can activate the anticancer immune response and is highly attractive to improve cancer treatment efficacy. ICD is closely related to endoplasmic reticulum (ER) stress, and a series of ICD inducers has recently been reported based on ER-targeted photodynamic/photothermal agents or metal complexes. However, these ER-targeted ICD inducers suffer from complicated synthesis and heavy-metal cytotoxicity. Inspired by the promising clinical potential of small organic molecules, herein, an ER-targeted fluorescent self-reporting ICD inducer, SA-Cbl, is developed by simple conjugation of the chemotherapeutic drug chlorambucil (Cbl) with salicylaldehyde (SA). SA-Cbl can selectively accumulate in the ER to induce rapid ROS generation and an unfolded protein response process, which leads to a fast release of damage-associated molecular patterns and efficient dendritic cells maturation. Meanwhile, the ER-targeted accumulation and ER-stress-inducing process can be in situ monitored based on the turn-on fluorescence of SA-Cbl, which is highly pH- and polarity-sensitive and can selectively interact with ER proteins. Compared with the traditional chemotherapy drug doxorubicin, the superior anticancer immunity effect of SA-Cbl is verified via an in vivo tumor model. This study thus provides a new strategy for developing fluorescent self-reporting ICD inducers by decoration of chemotherapeutic drugs with pH and polarity-sensitive organic fluorophores.
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