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

Sep 29, 2026

Triple-negative breast cancer (TNBC) presents a major therapeutic challenge due to its immunosuppressive complexity and lack of hormone receptors, limiting conventional treatment options. The STING (stimulator of interferon genes) pathway offers a route to convert immunogenic “cold” TNBC into “hot” tumors, improving sensitivity to immune checkpoint blockade. Clinical translation remains constrained by inadequate cytosolic delivery, rapid systemic degradation, and tumor microenvironment-driven metabolic inactivation. This review summarizes advances in STING-mediated nanoparticle delivery, including biomimetic and stimuli-responsive systems, and discusses mechanisms linking ferroptosis, cuproptosis, and mitochondrial DNA disruption to type I interferon amplification and dendritic cell maturation, highlighting synergy with ICB.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages23

Reading Time58 min

AccessFree to download

Review overview

STING pathway and TNBC immunogenic conversion

Barriers to clinical translation

STING-mediated nanoparticle delivery strategies

Mechanistic immune activation and synergy with ICBs

DOI: 10.1002/ctm2.70580 REVIEW Stimulator of interferon genes (STING)-activating nanomedicines: Translating innate immune modulation into effective therapy for triple-negative breast cancer Harshita Singhai1 Taha Alqahtani2 Humood Al Shmrany3 Garima Gupta4, 5 Umesh Kumar Patil1 Amirhossein Sahebkar6 Prashant Kesharwani1 1 Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya (A Central University), Sagar, Madhya Pradesh, India 2 Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, Saudi Arabia 3 Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia 4 Graphic Era Hill University, Dehradun, India 5 School of Allied Medical Sciences, Lovely Professional University, Phagwara, Punjab, India 6 Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran Correspondence Amirhossein Sahebkar, Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. [Email:](Email: amir_saheb2000@yahoo.com)[ amir_saheb2000@yahoo.com](Email: amir_saheb2000@yahoo.com) Umesh Kumar Patil, Prashant Kesharwani, Department of Pharmaceutical Sciences, Dr. Harisingh GourVishwavidyalaya (A Central University), Sagar, Madhya Pradesh, India. [Email:](Email: prashantdops@gmail.com)[ prashantdops@gmail.com](Email: prashantdops@gmail.com), [umeshpatil29@gmail.com](umeshpatil29@gmail.com) Graphical Abstract Graphical representation of STING-activated nanomedicines is for effective treatment of triple-negative breast cancer. Clin. Transl. Med. 2026;16:e70580 . [https://doi.org/10.1002/ctm2.70580](https://doi.org/10.1002/ctm2.70580) [wileyonlinelibrary.com/journal/ctm2](wileyonlinelibrary.com/journal/ctm2) DOI: 10.1002/ctm2.70580 REVIEW Stimulator of interferon genes (STING)-activating nanomedicines: Translating innate immune modulation into effective therapy for triple-negative breast cancer Harshita Singhai1 Taha Alqahtani2 Humood Al Shmrany3 Garima Gupta4, 5 Umesh Kumar Patil1 Amirhossein Sahebkar6 Prashant Kesharwani1 1 Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya (A Central University), Sagar, Madhya Pradesh, India 2 Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, Saudi Arabia 3 Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia 4 Graphic Era Hill University, Dehradun, India 5 School of Allied Medical Sciences, Lovely Professional University, Phagwara, Punjab, India 6 Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran Correspondence Amirhossein Sahebkar, Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. Email: [amir_saheb2000@yahoo.com](amir_saheb2000@yahoo.com) Umesh Kumar Patil, Prashant Kesharwani, Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya (A Central University), Sagar, Madhya Pradesh, India. [Email:](Email: prashantdops@gmail.com)[ prashantdops@gmail.com](Email: prashantdops@gmail.com), [umeshpatil29@gmail.com](umeshpatil29@gmail.com) Funding information Prince sattam bin Abdulaziz University, Grant/Award Number: PSAU/2025/R/1447; Deanship of Scientific Research at King Khalid University, Grant/Award Number: RGP2/413/46 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

FAQs

What makes triple-negative breast cancer difficult to treat in conventional therapy?

TNBC has profound immunosuppressive complexity and lacks hormone receptors, removing eligibility for hormone-based conventional therapies and contributing to treatment resistance.

How does the STING pathway aim to improve TNBC immunotherapy?

STING signaling can convert immunologically “cold” TNBC tumors into “hot” tumors, increasing responsiveness to immune checkpoint blockade by enhancing innate immune activation.

Which delivery and tumor microenvironment factors hinder clinical translation of STING activation?

Insufficient cytosolic delivery, rapid systemic degradation, and tumor microenvironment-induced metabolic inactivation reduce effective STING engagement in patients.

Sep 29, 2026

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