Stable and Biocompatible Cellulose-Based CaCO3 Microspheres for Tunable pH-Responsive Drug Delivery

Controlling the structure, particularly the structure template stability, has great potential for the fabrication of high-capacity and renewable drug carriers. Herein, novel porous CaCO3 microspheres about 2–3.5 μm with hollow cellulose nanoparticles (NPs, diameter centered at 15–35 nm) as templates were first assembled, with a highly specific surface area of ∼363 m2/g. The hollow cellulose NPs were previously prepared by the water-soluble dialdehyde cellulose, followed by the reduction of l-arginine (RDACws). Such self-assembled CaCO3 microspheres showed outstanding stability, which could retain high porosity for over 4 weeks under ethanol storage conditions, due to the electrostatic interactions between Ca2+ and the preassembled RDACws nanostructures. Furthermore, the porous CaCO3 microspheres as potential drug carriers showed good encapsulation efficiency, excellent pH responsiveness (pH = 2.0 ≫ 7.4), and good biocompatibility, which could control the drug release at a specific location. The CaCO3 microspheres regulated by sustainable hollow cellulose NPs put forward for the first time a sustained drug release, demonstrating that the cellulose hollow NPs together with the mineralization theory bring a brilliant prospect to biomineral materials.