STING agonist delivery by tumour-penetrating PEG-lipid nanodiscs primes robust anticancer immunity

Dane, Eric L.; Belessiotis‐Richards, Alexis; Backlund, Coralie M.; Wang, Jianing; Hidaka, Kousuke; Milling, Lauren E.; Bhagchandani, Sachin; Melo, Mariane B.; Wu, Shengwei; Li, Na; Donahue, Nathan D.; Ni, Kaiyuan; Ma, Leyuan; Okaniwa, Masanori; Stevens, Molly M.; Alexander‐Katz, Alfredo; Irvine, Darrell J.

doi:10.1038/s41563-022-01251-z

articleNature MaterialsMay 23, 2022HYBRID OA

STING agonist delivery by tumour-penetrating PEG-lipid nanodiscs primes robust anticancer immunity

ELEric L. Dane ABAlexis Belessiotis‐Richards CMCoralie M. Backlund JWJianing Wang KHKousuke Hidaka

Massachusetts Institute of Technology · NIHR Imperial Biomedical Research Centre · +6 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

Activation of the innate immune STimulator of INterferon Genes (STING) pathway potentiates antitumour immunity, but systemic delivery of STING agonists to tumours is challenging. We conjugated STING-activating cyclic dinucleotides (CDNs) to PEGylated lipids (CDN-PEG-lipids; PEG, polyethylene glycol) via a cleavable linker and incorporated them into lipid nanodiscs (LNDs), which are discoid nanoparticles formed by self-assembly. Compared to state-of-the-art liposomes, intravenously administered LNDs carrying CDN-PEG-lipid (LND-CDNs) exhibited more efficient penetration of tumours, exposing the majority of tumour cells to STING agonist. A single dose of LND-CDNs induced rejection of established tumours,…

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Topics & keywords

Topics

Keywords

Sting
Stimulator of interferon genes
PEG ratio
Linker
Polyethylene glycol
Agonist
Immunotherapy
Cancer research

UN Sustainable Development Goals

Good health and well-being

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