背向效应
TLR7型
免疫检查点
癌症研究
封锁
免疫系统
医学
免疫原性细胞死亡
免疫疗法
癌症
纳米医学
转移
放射治疗
免疫学
先天免疫系统
受体
内科学
材料科学
Toll样受体
纳米颗粒
纳米技术
作者
Qi Lu,Qiang Sun,Peishan Li,Lifang Yang,Shan Yang,Yidan Wang,Yating Cheng,Yilin Song,Siyu Wang,Fengping Tan,Nan Li
摘要
Photothermal therapy (PTT) has shown promising potential and bright prospects in damaging primary tumors; however, it is limited to metastatic and recrudescent tumors as PTT requires straightforward light irradiation. Moreover, metastatic and recrudescent tumor immunosuppression due to host T-cell antitumor activity is dramatically impeded because of programmed cell death 1 ligand (PD-L1) and programmed cell death receptor 1 (PD-1) pathways and immune checkpoint blockade (ICB) therapy. In this work, we demonstrate that PTT combined with ICB could not only eliminate primary tumors, but also prevent tumor metastasis to the lungs/liver. In particular, we have designed immunoadjuvant nanomedicine carriers on the basis of polydopamine (PDA) simultaneously loaded with resiquimod (R848)-a kind of toll-like receptor 7 (TLR7) agonist-and carbon dots (CDs)-a fluorescent agent. This nanomedicine is defined as PDA-PEG-R848-CD nanoparticle (NP). The multitasking PDA-PEG-R848-CD NPs can destroy 4T1 breast tumors by PTT under near-infrared laser irradiation in addition to generating tumor-associated antigens. Moreover, the PTT effect triggered the release of R848, thereby inducing a strong antitumor immune response. Meanwhile, this synergistic therapy also shows the abscopal effects by completely inhibiting the growth of untreated distant tumors by effectively triggering the tumors infiltrated by CD3/CD8. Such findings suggest that PDA-PEG-R848-CD NPs could 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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