An Activatable AIEgen Probe for High-Fidelity Monitoring of Overexpressed Tumor Enzyme Activity and Its Application to Surgical Tumor Excision

Monitoring fluctuations in enzyme overexpression facilitates early tumor detection and excision. An AIEgen probe (DQM-ALP) for the imaging of alkaline phosphatase (ALP) activity was synthesized. The probe consists of a quinoline-malononitrile (QM) core decorated with hydrophilic phosphate groups as ALP-recognition units. The rapid liberation of DQM-OH aggregates in the presence of ALP resulted in aggregation-induced fluorescence. The up-regulation of ALP expression in tumor cells was imaged using DQM-ALP. The probe permeated into 3D cervical and liver tumor spheroids for imaging spatially heterogeneous ALP activity with high spatial resolution on a two-photon microscopy platform, providing the fluorescence-guided recognition of sub-millimeter tumorigenesis. DQM-ALP enabled differentiation between tumor and normal tissue ex vivo and in vivo, suggesting that the probe may serve as a powerful tool to assist surgeons during tumor resection.     

Lanthanide‐Doped LiLuF4 Upconversion Nanoprobes for the Detection of Disease Biomarkers

Lanthanide‐doped upconversion nanoparticles (UCNPs) have shown great promise in bioapplications. Exploring new host materials to realize efficient upconversion luminescence (UCL) output is a goal of general concern. Herein, we develop a unique strategy for the synthesis of novel LiLuF₄:Ln³⁺ core/shell UCNPs with typically high absolute upconversion quantum yields of 5.0 % and 7.6 % for Er³⁺ and Tm³⁺, respectively. Based on our customized UCL biodetection system, we demonstrate for the first time the application of LiLuF₄:Ln³⁺ core/shell UCNPs as sensitive UCL bioprobes for the detection of an important disease marker β subunit of human chorionic gonadotropin (β‐hCG) with a detection limit of 3.8 ng mL⁻¹, which is comparable to the β‐hCG level in the serum of normal humans. Furthermore, we use these UCNPs in proof‐of‐concept computed tomography imaging and UCL imaging of cancer cells, thus revealing the great potential of LiLuF₄:Ln³⁺ UCNPs as efficient nano‐bioprobes in disease diagnosis.     

Graphene‐Oxide‐Modified Lanthanide Nanoprobes for Tumor‐Targeted Visible/NIR‐II Luminescence Imaging

The synthesis of hydrophilic lanthanide‐doped nanocrystals (Ln³⁺‐NCs) with molecular recognition ability for bioimaging currently remains a challenge. Herein, we present an effective strategy to circumvent this bottleneck by encapsulating Ln³⁺‐NCs in graphene oxide (NCs@GO). Monodisperse NCs@GO was prepared by optimizing GO size and core–shell structure of NaYF₄:Yb,Er@NaYF₄, thus combining the intense visible/near‐infrared II (NIR‐II) luminescence of NCs and the unique surface properties and biomedical functions of GO. Such nanostructures not only feature broad solvent dispersibility, efficient cell uptake, and excellent biocompatibility but also enable further modifications with various agents such as DNA, proteins, or nanoparticles without tedious procedures. Moreover, we demonstrate in proof‐of‐concept experiments that NCs@GO can realize simultaneous intracellular tracking and microRNA‐21 visualization, as well as highly sensitive in vivo tumor‐targeted NIR‐II imaging at 1525 nm.