PH-Responsive STING-Activating DNA Nanovaccines for Cancer Immunotherapy.

ABSTRACT: Cyclic dinucleotides (CDNs), such as c-di-GMP (CDG), are agonists for stimulator of interferon genes (STING) and are promising for cancer immunotherapy. Yet, the therapeutic efficacy of CDNs has been limited by poor delivery and biostability. Here, STING-activating DNA nanovaccines (STING-NVs) are developed, which biostabilize, deliver, and conditionally release CDG in the endosome of immune cells, elicit potent antitumor immune responses in murine and human immune cells, ameliorate immunosuppression in vitro and in the tumor microenvironment, and mediate potent cancer immunotherapy in a murine melanoma model. STING-NVs have PLA-b-PEG in the core and cytosine (C)-rich i-motif DNA on the surface. i-Motif DNA undergoes characteristic pH-responsive conformational switch, allowing effic

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC8323737 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature