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Dual-Blockade Immune Checkpoint for Breast Cancer Treatment Based on a Tumor-Penetrating Peptide Assembling Nanoparticle
journal contribution
posted on 2019-10-18, 17:45 authored by Guorui Li, Yuan Gao, Chunai Gong, Zhimin Han, Lei Qiang, Zongguang Tai, Jing Tian, Shen GaoCancer immunotherapy
can enhance the antitumor effect of drugs
through a combinatorial approach in a synergistic manner. However,
the effective targeted delivery of various drugs remains a challenge.
We generated a peptide assembling tumor-targeted nanodelivery system
based on a breast cancer homing and penetrating peptide for the codelivery
of a programmed cell death ligand 1 (PD-L1) small interfering RNA
(siRNA) (siPD-L1) and an indoleamine 2,3-dioxygenase inhibitor as
a dual blockade of an immune checkpoint. The vector is capable of
specifically accumulating in the breast cancer tumor site in a way
that allows the siRNA to escape from endosomal vesicles after being
endocytosed by tumor cells. The drug within these cells then acts
to block tryptophan metabolism. The results showed that locally released
siPD-L1 and 1-methyl-dl-tryptophan favor the survival and
activation of cytotoxic T lymphocytes, resulting in apoptosis of breast
cancer cells. Therefore, this study provides a potential approach
for treating breast cancer by blocking immunological checkpoints through
the assembly of micelles with functional peptides.
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breast cancer cellsBreast Cancer TreatmentTumor-Penetrating Peptide Assembling Nanoparticle Cancer immunotherapy1- methyl-dl-tryptophan favorbreast cancer tumor siteDual-Blockade Immune CheckpointPD-LsiRNAtumor-targeted nanodelivery systemsiPD-Lblock tryptophan metabolismapproachcell death ligand 1peptidecytotoxic T lymphocytesbreast cancerRNA
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