Work

Angiopep-2 functionalized poly(lactic-co-glycolic acid) nanocomposite for synergistic chemo-immunotherapy in glioma through STING pathway activation

Year: 2026

Type: article

Abstract: Effective treatment of glioma remains challenging due to the limited permeability of the blood–brain barrier (BBB) and the highly immunosuppressive tumor microenvironment. To address these obstacles, we develop a multifunctional nanocomposite, Ang-PMT, that enables synergistic chemo-immunotherapy by enhancing BBB penetration and amplifying activation of the stimulator of interferon genes (STING) pathway. Ang-PMT consists of poly(lactic-co-glycolic acid) (PLGA) conjugated with angiopep-2 (Ang) and encapsulates manganese dioxide (MnO 2 ) nanoparticles and triphenylphosphonium modified doxorubicin (TPP-DOX). Ang-PMT efficiently traverses the BBB via Ang-mediated transcytosis and selectively targets glioma cells through mitochondrial localization conferred by the TPP moiety. Upon exposure to intracellular glutathione, Ang-PMT rapidly degrades, releasing DOX and generating Mn 2+ ions that synergistically activate STING signaling and induce immunogenic cell death, thereby amplifying therapeutic efficacy. Consequently, Ang-PMT enables precise drug delivery and achieves potent synergistic inhibition of tumor growth, significantly outperforming TPP-DOX, Ang-PM, and Ang-PT treatments.

Source: Materials & Design

DOI: 10.1016/j.matdes.2026.115649