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ACS Appl Mater Interfaces. 2018 May 30;10(21):17582-17593. doi: 10.1021/acsami.8b02954. Epub 2018 May 15.

Enhanced Tumor Retention Effect by Click Chemistry for Improved Cancer Immunochemotherapy.

Author information

1
Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy , Sichuan University . No. 17, Block 3, Southern Renmin Road , Chengdu 610041 , China.

Abstract

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 achieved because of the reduced PD-L1 expression and regulatory T cells. In addition, effective long-term immunity from memory T cell responses protected mice from tumor recurrence.

KEYWORDS:

click chemistry; drug delivery; immune checkpoint inhibitor; immunochemotherapy; immunogenic cell death (ICD)

PMID:
29738228
DOI:
10.1021/acsami.8b02954
[Indexed for MEDLINE]

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