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A Novel Type of Aqueous Dispersible Ultrathin-Layered Double Hydroxide Nanosheets for in Vivo Bioimaging and Drug Delivery.

Layered double hydroxide (LDH) nanoparticles have been widely used for various biomedical applications. However, because of the difficulty of surface functionalization of LDH nanoparticles, the systemic administration of these nanomaterials for in vivo therapy remains a bottleneck. In this work, we develop a novel type of aqueous dispersible two-dimensional ultrathin LDH nanosheets with a size of about 50 nm and a thickness of about 1.4 to 4 nm. We are able to covalently attach positively charged rhodamine B fluorescent molecules to the nanosheets, and the nanohybrid retains strong fluorescence in liquid and even dry powder form. Therefore, it is available for bioimaging. Beyond this, it is convenient to modify the nanosheets with neutral poly(ethylene glycol) (PEG), so the nanohybrid is suitable for drug delivery through systemic administration. Indeed, in the test of using these nanostructures for delivery of a negatively charged anticancer drug, methotrexate (MTX), in a mouse model, dramatically improved therapeutic efficacy is achieved, indicated by the effective inhibition of tumor growth. Furthermore, our systematic in vivo safety investigation including measuring body weight, determining biodistribution in major organs, hematology analysis, blood biochemical assay, and hematoxylin and eosin stain demonstrates that the new material is biocompatible. Overall, this work represents a major development in the path of modifying functional LDH nanomaterials for clinical applications.

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