# Stimulator of interferon genes (STING)‐activating nanomedicines: Translating innate immune modulation into effective therapy for triple‐negative breast cancer

## TL;DR

This paper reviews how STING-activating nanomedicines can transform cold TNBC tumors into responsive ones, improving cancer treatment through immune activation.

## Contribution

The paper highlights novel nanoparticle delivery systems that enhance STING activation and synergize with immunotherapies for TNBC.

## Key findings

- Nanoparticles improve STING activation by overcoming delivery and degradation issues in the tumor microenvironment.
- Biomimetic and stimuli-responsive systems boost type I interferon and dendritic cell maturation.
- Combining STING-activating nanomedicines with ICBs enhances antitumor immune responses.

## Abstract

Triple‐negative breast cancer (TNBC), marked by profound immunosuppressive complexity, poses a critical challenge in therapy due to the absence of hormone receptors in its phenotype, making it unavailable for conventional therapies. The stimulator of interferon genes (STING) pathway is emerging as critical pathway translating the immunogenic ‘cold’ TNBC tumour into ‘hot’ one, thereby improving the responsiveness to immune checkpoint blockade (ICB). However, the clinical translation is still hindered by insufficient cytosolic delivery, rapid systemic degradation and tumour microenvironment‐induced metabolic inactivation. This review outlines the recent advances in STING‐mediated nanoparticle delivery with special emphasis on biomimetic, Trojan horse logic gate, manganese‐based and redox‐responsive stimuli delivery systems. Mechanistically, it integrates immune activation by ferroptosis, cuproptosis and mitochondrial DNA disruption. They synergise the amplification of type 1 interferon with dendritic cell maturation, potentiating antitumour immunogenesis. Notably, the combination with ICBs will further amplify the therapeutic potential of nanoparticles. Convergence of immunology and targeted therapies with nanoparticles opens new array for TNBC treatment. The review visualizes the clinical translation of mind maps into clinical reality, activating the innate immunity.

STING activation converts immunologically cold TNBC into ICB‐responsive hot tumors.Nanoparticles overcome poor delivery, degradation, and TME‐driven STING inactivation.Biomimetic and stimuli‐responsive systems enhance type I IFN and DC maturation.Synergy with ICBs boosts innate immunity and antitumor immunogenesis.

STING activation converts immunologically cold TNBC into ICB‐responsive hot tumors.

Nanoparticles overcome poor delivery, degradation, and TME‐driven STING inactivation.

Biomimetic and stimuli‐responsive systems enhance type I IFN and DC maturation.

Synergy with ICBs boosts innate immunity and antitumor immunogenesis.

Graphical representation of STING‐activated nanomedicines is for effective treatment of triple‐negative breast cancer.