Highly Efficient and Long-Lasting Chemiluminescence-Functionalized Nanohydrogel for Imaging-Guided Precise Piperlongumine Chemotherapy.

A major challenge for imaging-guided precise chemotherapy remains the ability to track the in situ real-time variation of the reactive oxygen species (ROS) level during treatment with prooxidation antitumor drugs. Chemiluminescence (CL) is widely used as an imaging tool with an excellent signal-to-noise ratio and high biological safety. However, suffering from flash-type and poor water solubility, most of the reported CL probes for ROS detection are unsuitable for in vivo long-term tracking. Herein, we designed a water-soluble CL nanohydrogel (L-012/Co@NGs) by cross-linking of vinyl-derived β-cyclodextrin monomer (MAH-β-CD) and loaded with luminol analog L-012 and cobalt ions (Co). studies reveal that L-012/Co@NGs exhibit long-lasting CL emission (up to 4 h) due to the slow diffusion of hydrogen peroxide in the nanohydrogel. High catalytic efficiency from the accelerated reduction of Co to Co through Tris and chelation of Co, as well as protection of the β-CD cavity against the active intermediate of L-012, enables L-012/Co@NGs to exhibit a 722-fold CL signal turn-on ratio and a nanomolar limit of detection (8.9 nmol/L). Piperlongumine (PL) was selected as a model of prooxidation drugs. The long-term and highly efficient CL strategy was designed for monitoring the local dynamic changes of ROS in PL-treated tumor-bearing mice for 150 min. The CL signal increased over time until reaching its maximum with a ∼6-fold increase at 15 min and then decreased slowly. The CL-functionalized nanohydrogel platform with good biocompatibility offers a great opportunity for imaging-guided precise tumor chemotherapy of PL and other prooxidation antitumor drugs.