Zhiping Cao,1,2 Haiyan Gao,2 Yong Xu1 

1Department of Clinical Psychology, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, People’s Republic of China; 2School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China

Correspondence: Haiyan Gao; Yong Xu, Email haiyangao@cuhk.edu.hk; xuyongsmu@vip.163.com

Purpose: The integration of multifunctional components into a single nanoplatform offers significant potential for personalized and minimally invasive therapeutic applications. Herein, we present a facile yet versatile strategy to engineer a near-infrared (NIR) pH- and light-responsive nanomaterial, demonstrating promising efficacy in glioblastoma combination therapy through multimodal synergistic mechanisms.
Methods: The FEID nanoplatform was engineered by co-assembling ICG, DOX, and Fe³⁺. Systematic characterization included physicochemical properties (TEM, DLS, UV-vis-NIR spectroscopy, zeta potential measurements, and XPS), photothermal conversion efficiency, Fenton reaction kinetics, PTT-enhanced CDT performance, laser-triggered drug release patterns, and NIR-responsive drug release and dual-modal imaging (fluorescence/MRI) capabilities. Intracellular DOX accumulation and ROS generation were confirmed by confocal laser scanning microscopy and flow cytometry in U87 glioma cells. Hemolysis assay, cytotoxicity profiling against normal 293T and RAW264.7 cells, and H&E staining were applied for biosafety assessment. The synergistic anti-glioblastoma efficacy was systematically evaluated through MTT assays, live/dead cell staining, and apoptosis detection via Annexin V/PI staining. The pharmacokinetic profiles and blood-brain barrier (BBB) permeability of the FEID were analyzed in vivo.
Results: The FEID nanoplatform displayed uniform spherical morphology (78.2 nm average diameter). pH/NIR-triggered release of DOX (chemotherapy) and ICG (PTT), combined with GSH depletion and NIR irradiation, synergistically enhanced Fe²⁺-mediated CDT. This multimodal therapy demonstrated potent cytotoxicity against U87 glioblastoma cells (14.8% cell viability). Furthermore, ICG fluorescence recovery and MRI contrast enabled tumor imaging, while enhanced BBB permeability ensured effective drug delivery for in situ glioma treatment.
Conclusion: In summary, we developed a safe FEID anti-tumor nanoplatform through a simple self-assembly process. This platform demonstrates the potential for controlled drug release and efficient combination therapy.

Keywords: intelligent drug delivery system, responsive drug release, fluorescence recovery, combination therapy