Opto-magnetic optimization enhances the multimodal therapeutic and diagnostic (UCL/T₁-T₂W MRI) potential of GdOF...

A novel Yb³⁺, Er³⁺ co-doped GdOF-based nanoprobe with integrated multimodal functionalities has been designed and optimized for simultaneous pH-responsive drug release, photothermal-photodynamic therapy (PTT-PDT), and dual-mode upconversion luminescence and magnetic resonance imaging. The nanoprobe comprises polydopamine (PDA)-coated Yb³⁺, Er³⁺ co-doped GdOF nanoparticles, functionalized with NH₂-PEG-NH₂ and hyaluronic acid (HA) to provide physical stability and impart CD44-targeting specificity, while doxorubicin (DOX) is loaded for chemotherapy. In this proof-of-concept demonstration, we show that upon 980 nm (0.1 W) near-infrared (NIR) laser irradiation, the system exhibits intense red UCL emission at 668 nm for cell imaging applications. Additionally, it functions effectively as a dual-mode MRI contrast agent with excellent relaxivity values (r₁ ∼ 9.7916 ± 2.06 and r₂ ∼ 14.7393 ± 0.89 mM^-1 s^-1 at 3T), providing sufficient information about the anatomic and cellular progress of the lesions. This developed nanoprobe also exhibits a pH-responsive DOX release mechanism and facilitates chemo-photothermal-photodynamic (chemo-photo) therapy under NIR exposure, demonstrating its potential as a next-generation non-invasive curative strategy against triple-negative breast cancer (TNBC). Our combined therapy reveals the apoptosis of cancer cells through a CD44-TP53-BAX-BCL2-CASP3 signalling cascade. Overall, this work sheds new light on the development of GdOF-based next-generation nanotheranostic agents with multiple real-time imaging modalities and precise spatio-temporal therapeutic properties suitable at the cellular level, thereby rendering them a sensitive and specific treatment strategy for TNBC.