PO.CH01.04 · 化学
细胞外囊泡介导的FSL-1与LY2157299共递送用于小细胞肺癌肝转移的免疫治疗
Extracellular vesicle-mediated co-delivery of FSL-1 and LY2157299 for immunotherapy of small-cell lung cancer liver metastases
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作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
小细胞肺癌（SCLC）常转移至肝脏，在肝脏中以巨噬细胞为主导的免疫抑制维持肿瘤生长。对SCLC肝转移灶的生物信息学分析提示巨噬细胞代谢是肝脏进展的驱动因素。我们构建了共递送FSL-1（TLR2/6激动剂）和LY2157299/galunisertib（TGF-betaRI抑制剂）的细胞外囊泡（EV），以重编程巨噬细胞。体外实验中，双载EV更有效地使巨噬细胞向促炎、抗原呈递状态转变。体内实验中，EV高效靶向肝内肿瘤部位，减少肝肿瘤生长，并延长小鼠生存期。这些数据支持将EV介导的FSL-1与LY2157299共递送作为一种以巨噬细胞为中心的SCLC肝转移治疗策略。
查看英文原文 English abstract
Small-cell lung cancer (SCLC) frequently metastasizes to the liver, where macrophage‑dominated immunosuppression sustains tumor outgrowth. Bioinformatic analyses of SCLC liver metastases implicate macrophage metabolism as a driver of hepatic progression. We engineered extracellular vesicles (EVs) co‑delivering FSL‑1 (TLR2/6 agonist) and LY2157299/galunisertib (TGF‑betaRI inhibitor) to reprogram macrophages. In vitro, dual‑loaded EVs more efficiently shifted macrophages toward pro‑inflammatory, antigen‑presenting states. In vivo, EVs efficiently targeted intrahepatic tumor sites, decreased liver tumor growth, and prolonged mouse survival. These data support EV‑mediated co‑delivery of FSL‑1 and LY2157299 as a macrophage‑centric strategy for SCLC liver metastasis.
利益披露 Disclosure
Y. Huang, None.