Industrially synthesized biosafe vaterite hollow CaCO3 for controllable delivery of anticancer drugs

Calcium carbonate (CaCO 3 ) has been widely studied as a drug delivery system (DDS), but it still has some limitations in its clinical application in tumor chemotherapy, such as difficult industrialization, complex synthesis methods, time-consuming and labor-intensive, and low drug loading. Here, we developed an industrialized method for the simple, rapid and controllable synthesis of high drug-loaded vaterite hollow CaCO 3 (VHC). The VHC was successfully prepared by adding L-Leucine (Leu) in the process of preparing CaCO 3 in an industrial method. The effects of different reaction conditions on VHC were studied in detail, and a possible formation mechanism of VHC was proposed. As an industrially synthesized DDS, the VHC had low cytotoxicity and good biocompatibility, and had higher loading capacity (39.68%) and encapsulation efficiency (90.17%) for doxorubicin hydrochloride (DOX) due to the existence of hollow nano-cavity. Meanwhile, DOX@VHC showed good pH responsiveness, which can achieve sustained release of DOX. And, DOX@VHC could significantly inhibit tumor cells (cell inhibitory rate: 91.73%) and reduce the toxicity to normal cells. The high drug-loaded VHC synthesized rapidly by industrial methods can achieve controllable drug delivery and high-efficiency inhibition of tumor cells, and has a good application prospect in tumor therapy.