期刊
ACS APPLIED MATERIALS & INTERFACES
卷 10, 期 21, 页码 17582-17593出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.8b02954
关键词
drug delivery; click chemistry; immunochemotherapy; immune checkpoint inhibitor; immunogenic cell death (ICD)
资金
- Major projects of the National Natural Science Foundation of China [81690261]
- National Natural Science Foundation of China [81773658]
Because of the limited drug concentration in tumor tissues and inappropriate treatment strategies, tumor recurrence and metastasis are critical challenges for effectively treating malignancies. A key challenge for effective delivery of nanoparticles is to reduce uptake by reticuloendothelial system and to enhance the permeability and retention effect. Herein, we demonstrated Cu(I)-catalyzed click chemistry triggered the aggregation of azide/alkyne-modified micelles, enhancing micelles accumulation in tumor tissues. In addition, combined doxorubicin with the adjuvant monophosphoryl lipid A, an agonist of toll-like receptor4, generated immunogenic cell death, which further promoted maturity of dendritic cells, antigen presentation and induced strong effector T cells in vivo. Following combined with anti-PD-L1 therapy, substantial antitumor and metastasis inhibitory effects were the reduced PD-L1 expression and regulatory T cells. In addition, effective long-term immunity from memory T protected mice from tumor recurrence.
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