Premium
Design of an Injectable Polypeptide Hydrogel Depot Containing the Immune Checkpoint Blocker Anti‐PD‐L1 and Doxorubicin to Enhance Antitumor Combination Therapy
Author(s) -
Shi Yingge,
Li Dong,
He Chaoliang,
Chen Xuesi
Publication year - 2021
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.202100049
Subject(s) - doxorubicin , blockade , pharmacology , cancer research , immune checkpoint , cytotoxic t cell , immune system , melanoma , combination therapy , chemistry , pd l1 , programmed cell death , medicine , chemotherapy , immunotherapy , immunology , apoptosis , receptor , in vitro , biochemistry
Combination therapy can be used to enhance the therapeutic response and decrease side effects during cancer treatment. In this study, a system is developed to locally deliver the immune checkpoint blockade antibody targeting programmed death‐ligand 1 (anti‐PD‐L1 or aPD‐L1) and doxorubicin (Dox), by an injectable, biocompatible polypeptide hydrogel as a drug depot. The localized and sustained release of Dox after the intratumoral injection of the co‐loaded hydrogel induces immunogenic tumor cell death, thus promoting an antitumor immunological response. The tumor inhibitory effect is significantly enhanced by the simultaneous release of aPD‐L1 at the tumor site thanks to its action on the inhibition of the PD‐1/PD‐L1 pathway and restoration of the tumor‐killing effect of cytotoxic T cells. Treatment of the B16F10 melanoma model with the aPD‐L1 and Dox co‐loaded hydrogel leads to a remarkable inhibition of tumor progression and prolongation of animal survival.