A bottom-up synthesis of rare-earth-hydrotalcite monolayer nanosheets toward multimode imaging and synergetic therapy

Recently, ultrathin two-dimensional (2D) nanomaterials have attracted considerable research interest in biomedical applications, owing to their intriguing quantum size and surface effects. In this work, a one-step "bottom-up" method is developed to prepare rare-earth (Gd³⁺ and Yb³⁺) co-doped layered double hydroxide (LDH) monolayer nanosheets, with a precisely controlled composition and uniform morphology. Due to the successful introduction of Gd³⁺ and Yb³⁺ into the LDH host layer, the Gd&Yb-LDH monolayer nanosheets exhibit excellent magnetic resonance (MR)/X-ray computed tomography (CT) dual-mode imaging functionality. Moreover, the Gd&Yb-LDH monolayer nanosheets achieve an ultrahigh loading of a chemotherapeutic drug (SN38) with a loading content (LC) of 925%, which is a one order of magnitude enhancement compared with previously reported delivery systems of hydrophobic drugs. Interestingly, by further combination with indocyanine green (ICG), in vivo tri-mode imaging, including CT, MR and near infrared fluorescence (NIRF) imaging, is achieved, which enables a noninvasive visualization of cancer cell distribution with deep spatial resolution and high sensitivity. In addition, in vitro and in vivo therapeutic evaluations demonstrate an extremely high tri-mode synergetic anticancer activity and superior biocompatibility of SN38&ICG/Gd&Yb-LDH. Therefore, this work demonstrates a paradigm for the synthesis of novel multifunctional 2D monolayer materials via a facile "bottom-up" route, which shows promising applications in cancer synergetic theranostics.