Methotrexate intercalated calcium carbonate nanostructures: Synthesis, phase transformation and bioassay study

• MTX is served as both the target drug and effective complex agents to modify and control the morphology.
• ACC-MTX presents high drug-loading and excellent anticancer effect.
• The biodegradation of MTX-ACC was due to the synergy effect of drug release and the phase transformation.

The formation and stabilization of amorphous calcium carbonate (ACC) is an active area of research owing to the presence of stable ACC in various biogenic minerals. In this paper, the synthesis of calcium carbonate (CaCO3) under the participation of methotrexate (MTX) via a facile gas diffusion route was reported. The results indicated that the addition of MTX can result in the phase transformation of CaCO3, and then two kinds of hybrids, i.e., MTX-vaterite and stable MTX-ACC came into being. Interestingly, the functional agent MTX served as both the target anticancer drug loaded and effective complexation agents to modify and control the morphology of final samples. The examination of MTX-ACC biodegradation process revealed that the collapse of MTX-ACC nanoparticles was due to the synergistic effect of drug release and the phase transformation. Finally, our study also proved that MTX-ACC exhibited the most excellent suppressing function on the viability of cancer cells, especially after long-time duration.

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