Theranostic Folate-Targeted Doxorubicin-Loaded MIL-88A@CuFe ₂ O ₄ Nanohybrids, a pH-Sensitive, Core–Shell, Mesoporous Drug Delivery Platform with Dual-Modal T1–T2MRI and Optical Imaging Contrast Properties: An In Vitro and In Vivo Cancer Study

Multifunctional magneto-theranostic nanoplatform, with integrate imaging and therapy in simple platform offer transformative potential for precision cancer management due to their strong magnetic properties, biocompatibility, and versatile theranostic capabilities. Here, we report for the first time the theranostic application of in situ mesoporous core-shell MIL-88A@CuFe₂O₄ nanohybrid, as an interesting smart platform for dual-mode T1-T2MRI and optical imaging with quantitative analysis, combined with pH-sensitive targeted drug delivery. The nanohybrid was fabricated via a simple in situ synthesis, where Fe (0) from the CuFe₂O₄ core serves as a Fe³⁺ source for MIL-88A shell crystallization in the presence of fumaric acid, producing a mesoporous structure with high porosity and strong magnetism. Fe³⁺ centers in the MIL-88A shell provide T1 contrast, while the CuFe₂O₄ core enhances both T1 and T2 signals, achieving robust dual-mode MRI (r₁ = 73.0 mM⁻¹ s⁻¹, r₂ = 700.9 mM⁻¹ s⁻¹). The mesoporous shell allows pH-sensitive controlled release of doxorubicin, and folate conjugation ensures active tumor targeting, while intrinsic doxorubicin fluorescence enables optical tracking of biodistribution in vivo. Comprehensive in vitro and in vivo evaluations demonstrated high biocompatibility, selective cancer cell uptake, effective pH-responsive drug release, dual-modal MRI and fluorescence contrast, and significant tumor growth inhibition in a triple-negative breast cancer (4T1) mouse model. The nanohybrid's combination of high porosity, strong magnetism, dual T1-T2MRI contrast, targeted drug delivery, and therapeutic efficacy distinguish it from existing theranostic agents. This work highlights a theranostic application of MIL-88A@CuFe₂O₄ nanohybrids, demonstrating their potential as a unique multifunctional platform for precise cancer diagnosis and treatment.