Remarkable NIR Enhancement of Multifunctional Nanoprobes for In Vivo Trimodal Bioimaging and Upconversion Optical/T₂‐Weighted MRI‐Guided Small Tumor Diagnosis

Effective nanoprobes and contrast agents are urgently sought for early‐stage cancer diagnosis. Upconversion nanoparticles (UCNPs) are considerable alternatives for bioimaging, cancer diagnosis, and therapy. Yb 3+ /Tm 3+ co‐doping brings both emission and excitation wavelengths into the near‐infrared (NIR) region, which is known as “optical transmission window” and ideally suitable for bioimaging. Here, NIR emission intensity is remarkably enhanced by 113 times with the increase of Yb 3+ concentration from 20% to 98% in polyethylene glycol (PEG) modified NaYF 4 :Yb 3+ /Tm 3+ UCNPs. PEG‐UCNPs‐5 (98% Yb 3+ ) can act as excellent nanoprobes and contrast agents for trimodal upconversion (UC) optical/CT/T 2 ‐weighted magnetic resonance imaging (MRI). In addition, the enhanced detection of lung in vivo long‐lasting tracking, as well as possible clearance mechanism and excretion routes of PEG‐UCNPs‐5 have been demonstrated. More significantly, a small tumor down to 4 mm is detected in vivo via intravenous injection of these nanoprobes under both UC optical and T 2 ‐weighted MRI modalities. PEG‐UCNPs‐5 can emerge as bioprobes for multi‐modal bioimaging, disease diagnosis, and therapy, especially the early‐stage tumor diagnosis.