Authors
Fangying Zheng, Yanyun Su, Xianbin Sun, Ding Tan, Ya Wang, Xiumei Li, Yu Gao
Published in
Materials today. Bio. Volume 39. Pages 103420. Epub Jun 29, 2026.
Abstract
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are primary treatments for EGFR-mutated non-small cell lung cancer (NSCLC), but acquired resistance limits efficacy. To address this challenge, we developed CsO/IGA, a multifunctional nanoplatform combining osimertinib (AZD9291) with an indocyanine green-gadolinium (ICG-Gd) probe via oleanolic acid (OA)-modified chitosan encapsulation, integrating fluorescence/magnetic resonance imaging (FLI/MRI) with chemo-phototherapy and tumor microenvironment (TME) modulation. CsO/IGA (∼100 nm) demonstrated excellent stability and generated both singlet oxygen and hyperthermia under 808 nm irradiation. The nanoplatform exerted efficient anti-cancer effects to overcome resistance through reactive oxygen species induction, mitochondrial membrane potential reduction, and EGFR/phosphorylated EGFR downregulation in sensitive and resistant NSCLC cells. Notably, the OA component suppressed cancer-associated fibroblasts and α-smooth muscle actin expression, remodeling the TME to enhance tumor penetration. In vivo studies confirmed tumor-specific accumulation and deep penetration, FLI/MRI capability, and superior antitumor efficacy through chemo-phototherapy synergy. This work presents a promising OA-integrated theranostic strategy integrating targeted therapy, phototherapy, TME modulation, and diagnostic imaging for overcoming EGFR-TKI resistance in NSCLC.
PMID:
42434729
Bibliographic data and abstract were imported from PubMed on 11 Jul 2026.
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