Under near-physiological pH, temperature, and ionic strength, amelogenin (Amel) accelerates hydroxyapatite (HAP) nucleation kinetics, decreasing the induction time in a concentrationdependent manner. Hierarchically organized apatite microstructures are achieved by self-assembly involving nucleated nanocrystallites and Amel oligomers and nanospheres at low supersaturations and protein concentrations in a slow and well-controlled constant composition (CC) system. The CC method allows the capture of an intermediate structure, the nanorod, following the formation of the critical nuclei at the earliest nucleation stages of calcium phosphate crystallization. The nanorod building blocks form spontaneously by synergistic interactions between flexible Amel protein assemblies and rigid calcium phosphate nanocrystallites. These intermediate structures further assemble by a self-epitaxial growth mechanism to form the final hierarchically organized microstructures that are compositionally and morphologically similar to natural enamel. This in vitro observation provides direct evidence that Amel promotes apatite crystallization and organization. We interpret our observations to propose that in vivo Amel may maximally exert an influence on the structural control of developing enamel crystals at the earliest nucleation stages.

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Drug delivery systems with targeting agents for precise drug release in cancer therapy are very significant and important. Herein, we report the rational design and synthesis of a DOX (doxorubicin) loaded UiO-68-type of nanoscale metal-organic framework (NMOF) with a tumor targeting agent (folic acid, FA), DOX@UiO-68-FA (3), as a multifunctional drug delivery system for hepatoma (Hep G2) therapy via tail-vein injection. Compared to free DOX, FA-unloaded DOX@Mi-UiO-68 (2), 3 exhibits a much higher antitumor efficacy, which was confirmed by cell imaging, standard 3-(4,5-dimethylthiahiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) proliferation and in vivo experiments.