Programmable co-delivery of the immune checkpoint inhibitor NLG919 and chemotherapeutic doxorubicin via a redox-responsive immunostimulatory polymeric prodrug carrier

Acta Pharmacologica Sinica
Jingjing SunSong Li

Abstract

To achieve synergistic therapeutic efficacy and prevent cancer relapse, chemotherapy and immunotherapy have been combined as a new modality for tumor treatment. In this work, we designed a redox-responsive immunostimulatory polymeric prodrug carrier, PSSN10, for programmable co-delivery of an immune checkpoint inhibitor NLG919 (NLG) and a chemotherapeutic doxorubicin (DOX). NLG-containing PSSN10 prodrug polymers were self-assembled into nano-sized micelles that served as a carrier to load DOX (DOX/PSSN10 micelles). DOX/PSSN10 micelles displayed spherical morphology with a size of ∼170 nm. DOX was effectively loaded into PSSN10 micelles with a loading efficiency of 84.0%. In vitro DOX release studies showed that rapid drug release could be achieved in the highly redox environment after intracellular uptake by tumor cells. In 4T1.2 tumor-bearing mice, DOX/PSSN10 micelles exhibited greater accumulation of DOX and NLG in the tumor tissues compared with other organs. The PSSN10 carrier dose-dependently enhanced T-cell immune responses in the lymphocyte-Panc02 co-culture experiments, and significantly inhibited tumor growth in vivo. DOX/PSSN10 micelles showed potent cytotoxicity in vitro against 4T1.2 mouse breast cancer cells and PC...Continue Reading

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Citations

Jun 23, 2018·Journal of Enzyme Inhibition and Medicinal Chemistry·Guangwei XuRong Xiang
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Methods Mentioned

BETA
column chromatography
fluorescence spectroscopy
fluorescence spectrometry
dynamic
transmission electron microscopy
fluorescence
PMA

Software Mentioned

Phoenix WinNonlin

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