Ultrasmall Quantum Dots with Broad‐Spectrum Metal Doping Ability for Trimodal Molecular Imaging

Abstract Development of efficient targeting nanomaterials is extremely challenging due to the nonspecific accumulation in immune tissues, such as the liver and the spleen. Ultrasmall nanoparticles (USNPs) could possess small molecule‐like in vivo pharmacokinetic profiles, coupled with integrated functions capacity, improving the molecular imaging efficiency, particularly in oncology. For nuclear imaging, radiometals are often incorporated into the structures of USNPs using chelator and chelator‐free strategies. However, the incorporated chelator may change the surface properties and in vivo behavior of UNSPs, while chelator‐free labeling strategies either involve complicated resynthesis or rely on the active properties of the metal ions. Herein, a novel chelator‐free and postsynthetic strategy for broad‐spectrum metal ion attachment is reported. The ultrasmall Ag 2 Se quantum dots (QDs) are developed with an active oxygen layer on the surface, allowing for facile incorporation of both active and inert metals with high labeling efficiency. The particles enable fluorescence, magnetic resonance imaging, and positron emission tomography (PET) trimodality imaging. After conjugation with targeting peptide, the probe yields a high tumor‐to‐muscle ratio of nine in PET imaging. Importantly, the QDs are predominantly excreted from body through the renal route within 12 h. This chelator‐free strategy opens an avenue for exploring broad‐spectrum radiometal isotope labeling and USNP‐based renal‐excreting imaging probes.