Sequential Treatment of Bioresponsive Nanoparticles Elicits Antiangiogenesis and Apoptosis and Synergizes with a CD40 Agonist for Antitumor Immunity.

ABSTRACT: The combination of antiangiogenesis and chemotherapy regimens with cancer immunotherapy has the potential to synergistically boost antitumor immunity. Herein, we report the construction of two bioresponsive nanoparticles, namely, Podo-NP and CbP-NP, comprising prodrugs of podophyllotoxin (Podo) and carboplatin, respectively. Sequential treatment with esterase-responsive Podo-NP, redox-sensitive CbP-NP, and a CD40 agonist promotes antitumor T cell response. Podo-NP suppresses angiogenesis by preventing proliferation and migration of endothelial cells, sprouting of neovessels, formation of tubules, and stabilization of newly formed vessels. Vascular endothelial growth factor blockade and endostatin stimulation normalize tortuous tumor vasculatures to allow efficient infiltration of effector

SUBMITTER: Ling X 

PROVIDER: S-EPMC8216770 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature