Harnessing for quantitative MRI, bioluminescence, chemo-magnetic hyperthermia, and near-infrared optical imaging of a magnetic nanotheranostic for <i>in vivo</i> passive targeted monitoring in colorectal cancer models

Colorectal cancer is the second foremost cause of cancer-related fatalities, but it is currently missing an effective treatment. For researchers, the ability to monitor therapeutic nanoparticles of interest within a living animal using non-invasive observation tools has been a futuristic idea for a long time. In this work, a multifunctional magnetic nanotheranostic functionalized with Cyanine 5.5 and Doxorubicin was tested to enhance bio-monitoring and therapy efficiency in an <i>in vivo</i> CT26 murine colon model <i>via</i> retro-orbital injection. The <i>in vivo</i> biodistribution was measured by near-infrared optical imaging, which showed that the nanotheranostic largely accumulated in the tumor with maximum uptake observed at the 3 h postinjection time point. This nanotheranostic was then metabolized and eliminated <i>via</i> the kidneys after 6 h and both the liver and spleen after 72 h of injection. Besides, the magnetic resonance imaging (MRI) modality with a specific <i>T</i>2*-weighted sequence demonstrates efficient nanoparticle accumulation within the tumor by the %<i>I</i>_0.25 quantitative method of hyposignal processing. Moreover, bioluminescence imaging demonstrated a significant chemotherapeutic effect after 72 h of injection of a 15 mg kg^-1 single dose. Hyperthermia treatment by AMF significantly impacts the synergistic efficiency of this second therapy provided by the Fe₃O₄ nanoparticle (NP) content. The resulting nanotheranostic demonstrated enhanced passive accumulation and selectively accumulated in the tumor with negligible distribution to adjacent healthy tissue, effectively suppressing tumor proliferation when combined with alternating magnetic field (AMF) stimulation. This powerful synergistic approach has proven to be a robust and versatile nanotheranostic for the effective treatment of colorectal cancer.