Biosens Bioelectron. 2026 Apr 15;298:118426. doi: 10.1016/j.bios.2026.118426. Epub 2026 Jan 20.
ABSTRACT
Disrupting mitochondrial homeostasis offers a promising strategy for treating lung adenocarcinoma (LUAD). However, its efficacy is limited by insufficient reactive oxygen species (ROS) generation and calcium ion accumulation. To amplify mitochondrial homeostasis disruption, the thermo/acid-responsive CaAuMn-capsaicin@PEG nanoreactor (CAMcaP) was designed. CAMcaP nanoreactor innovatively integrates calcium overload and photothermal enhanced ROS storm, coordinately disrupting mitochondrial homeostasis to offer a promising strategy for LUAD treatment. CAMcaP also serves as an excellent fluorescence/computed tomography (FL/CT) dual-mode imaging nanoprobe, enabling accurate localization of lesions and real-time monitoring of lesion changes during treatment. Specifically, CAMcaP integrates CaAuMn nanoparticles (CaAMNPs, serving as nanoprobe, photothermal agent, peroxidase-like enzyme and calcium donor) and capsaicin within DPPC-DSPE-PEG shell. After accumulating in tumors, hyperthermia triggers the disintegration of DPPC-DSPE-PEG shell under 808 nm laser irradiation (2.0 W/cm2,5 min), enabling controlled release of capsaicin and CaAMNPs. The acidic tumor microenvironment triggers CaAMNPs degradation to release Ca2+, while capsaicin opens transient receptor potential vanilloid 1 (TRPV1) channel on cancer cell membrane to induce intracellular calcium overload, thereby disrupting mitochondrial homeostasis. Meanwhile, CaAMNPs achieve nanocatalytic therapy via Mn2+-mediated Fenton-like reaction. Its photothermal performance further improves catalytic efficiency, and induces ROS storm that disrupts mitochondrial homeostasis, ultimately achieves tumor ablation. In conclusion, our work provides a visual diagnosis and intelligent treatment strategy for LUAD, integrating FL/CT dual-mode imaging with ion interference and photothermal enhanced ROS storm-induced mitochondrial homeostasis disruption.
PMID:41576433 | DOI:10.1016/j.bios.2026.118426