Yeast-Controlled Double-Shelled CaCO₃/CaF₂ Hollow Nanospheres with Hierarchically Porous for Sustained pH-Sensitive Drug Release

Hierarchically porous materials (HP materials) are believed one of the most hopeful matrix materials because of their distinctive multimodal pore structures and tremendous application potentials in the field of biomedicine. However, green and facile synthesis of hierarchically porous nanomaterials with beneficial water dispersibility and biocompatibility is still a great challenge. Herein, a novel biomimetic strategy is proposed to prepare the cell-tailored double-shelled HPCaCO3/CaF2 hollow nanospheres under the mediation of yeast cells. The biomolecules derived from the secretion of yeast cells are used as conditioning and stabilizing agents to control the biosynthesis of the HPCaCO3/CaF2 materials, which exhibit excellent water dispersibility and favorable biocompatibility. The double-shelled CaCO3/CaF2 nanospheres hold hierarchically porous structure and have abundant pore channel and large specific surface area, showing high drug-loading and a prolonged drug sustainable release profile by the pore-by-pore diffusion pattern of the hierarchical pores. Otherwise, the HPCaCO3 with pH-sensitivity could controllably release drug doxorubicin hydrochloride (DOX) at the acidic tumor microenvironment. Both in vitro and in vivo results demonstrate that HPCaCO3/CaF2 has the sustainable pH-sensitive drug release property, showing an enhanced therapeutic effect. Summarily, this study provides a biomimetic strategy to synthesize the hierarchically porous double-shelled hollow nanomaterials for applying in sustainable drug delivery system.