Opto-magnetic optimization enhances multimodal therapeutic and diagnostic (UCL/T1-T2W MRI) potentialities of GdOF against MDA-MB-231

Abstract

Novel Yb3+, Er3+ co-doped GdOF-based nanoprobe with integrated multimodal functionalities has been, designed, 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 endow physical stability and impart CD44-targeting specificity, while doxorubicin (DOX) is loaded for chemotherapy. We show in this proof of concept demonstration 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 application. Additionally, it functions effectively as a dual mode MRI contrast agent with excellent relaxivities values (r_1 ⁓ 9.7916 ± 2.06 and r_2 ⁓ 14.7393 ± 0.89 mM-1s-1 at 3T) endowing sufficient informations about anatomic and cellular progress of the lesions. This developed nanoprobe also exhibits a pH-responsive DOX release mechanism and facilitates chemo-photothermal-photodynamic therapy under NIR exposure affording its potentiality as next-generation non-invasive curative strategy against triple negative breast cancer (TNBC). Our combined therapy show apoptotic death cells through CD44-TP53-BAX-BCL2-CASP3 signalling in cascade. Overall, this work will shed new light on developing GdOF based next-generation nanotheranostic agent with multiple real-time imaging modalities and precise spatio-temporal therapeutic properties suitable at cellular level, thereby rendering them sensitive and specific TNBC treatment.