光热治疗
背向效应
免疫检查点
封锁
癌症研究
免疫系统
医学
免疫疗法
材料科学
免疫增强剂
癌症
伊米奎莫德
佐剂
PD-L1
癌症免疫疗法
肿瘤微环境
癌细胞
免疫学
无容量
药理学
受体
内科学
纳米技术
作者
Rui Ge,Cangwei Liu,Xue Zhang,Wenjing Wang,Binxi Li,Jie Liu,Yi Liu,Hongchen Sun,Daqi Zhang,Yuchuan Hou,Hao Zhang,Bai Yang
标识
DOI:10.1021/acsami.8b05876
摘要
Checkpoint blockade immunotherapy has shown great potential in clinical cancer therapy, but the body's systemic immune must be fully activated and generates a positive tumor-specific immune cell response. In this work, we demonstrate the design of the immune-adjuvant nanodrug carriers on the basis of poly(ethylene glycol)- block-poly(lactic- co-glycolic acid) copolymer-encapsulated Fe3O4 superparticles (SPs), in which imiquimod (R837), a kind of Toll-like receptor 7 agonist, is loaded. The nanodrug carriers are defined as Fe3O4-R837 SPs. The multitasking Fe3O4-R837 SPs can destroy the 4T1 breast tumor by photothermal therapy (PTT) under near-infrared laser irradiation to generate the tumor-associated antigens because of the high efficiency of tumor magnetic attraction ability and photothermal effect. The PTT also triggers the release of R837 as the adjuvant to trigger a strong antitumor immune response. By further combining with the checkpoint blockade adjusted by programmed death ligand 1 (PD-L1) antibody, the Fe3O4-R837 SP-involved PTT cannot only eliminate the primary tumors but also prevent tumor metastasis to lungs/liver. Meanwhile, this synergistic therapy also shows abscopal effects by completely inhibiting the growth of untreated distant tumors through effectively triggering the tumors infiltrated by CD45+ leukocytes. Such findings suggest that Fe3O4-R837 SP-involved PTT can significantly potentiate the systemic therapeutic efficiency of PD-L1 checkpoint blockade therapy by activating both innate and adaptive immune systems in the body.
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