Monolayer Nanosheets with an Extremely High Drug Loading toward Controlled Delivery and Cancer Theranostics

2D nanomaterials have attracted considerable research interest in drug delivery systems, owing to their intriguing quantum size and surface effect. Herein, Gd³⁺ -doped monolayered-double-hydroxide (MLDH) nanosheets are prepared via a facile bottom-up synthesis method, with a precisely controlled composition and uniform morphology. MLDH nanosheets as drug carrier are demonstrated in coloading of doxorubicin and indocyanine green (DOX&ICG), with an ultrahigh drug loading content (LC) of 797.36% and an encapsulation efficiency (EE) of 99.67%. This is, as far as it is known, the highest LC level at nearly 100% of EE among previously reported 2D drug delivery systems so far. Interestingly, the as-prepared DOX&ICG/MLDH composite material shows both pH-controlled and near-infrared-irradiation-induced DOX release, which holds a promise in stimulated drug release. An in vivo dual-mode imaging, including near-infrared fluorescence and magnetic resonance imaging, enables a noninvasive visualization of distribution profiles at the tumor site. In addition, in vitro and in vivo therapeutic evaluations demonstrate an excellent trimode synergetic anticancer activity and superior biocompatibility of DOX&ICG/MLDH. Therefore, MLDH nanosheets provide new perspectives in the design of multifunctional nanomedicine, which shows promising applications in controlled drug delivery and cancer theranostics.