Self-assembled supramolecular nanoparticles of α-mangostin for targeted STING activation and enhanced tumor immunotherapy.

Authors

Jiaqian Miao, Yuxin Liu, Sisi Chen, Yinxuan Zhou, Jun Liu, Danni Xu, Xuan Mo, Junjie Wang, Qianli Zhu, Chunyang Yu, Qiuhui Qian, Hongping Deng, Li Xu, Guangbo Ge

Published in

Acta pharmaceutica Sinica. B. Volume 16. Issue 9. Pages 6253-6273. Epub Jun 26, 2026.

Abstract

Targeted activation of the stimulator of interferon genes (STING) signaling pathway represents a promising strategy to counteract immunosuppressive tumor microenvironments (TME) and elicit anti-tumor immunity. However, clinical translation of STING agonists has been strongly hindered by the challenges in achieving tumor-targeted STING activation. Here, we report a facile and efficient supramolecular self-assembly strategy for tumor-targeted STING activation of α-mangostin (MGT), a natural non-cyclic dinucleotide STING agonist. MGT can self-assemble into uniform supramolecular nanoparticles (MGT-SNPs) with 100% drug loading, driven by its inherent amphiphilic xanthone structure via multiple non-covalent interactions. The resulting MGT-SNPs (∼186.50 nm, negatively charged) demonstrate excellent colloidal stability, pH-responsive drug release, and enhanced cellular uptake in vitro. Furthermore, MGT-SNPs exhibit sufficient circulatory stability, enabling efficient tumor accumulation and cytosolic delivery via the enhanced permeability and retention (EPR) effect. Leveraging these favorable properties, MGT-SNPs enhance STING activation both in vitro and in vivo, effectively remodeling TME. Consequently, MGT-SNPs trigger robust anti-tumor immunity in melanoma-bearing mice following either intratumoral or intravenous administration. Collectively, this work showcases a supramolecular self-assembly strategy based on the intrinsic structural properties of a STING agonist for tumor-targeted STING activation, which eliminates carrier-related toxicity and offers a clinically promising approach for STING-targeted cancer immunotherapy.

PMID:
42764994
Bibliographic data and abstract were imported from PubMed on 21 Sep 2026.

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