Biomineralization inspired synthesis of CaCO3-based DDS for pH-responsive release of anticancer drug

Calcium carbonate (CaCO 3 ) is an ideal candidate for use in drug delivery system (DDS) for cancer cure due to good biocompatibility, pH-sensitivity and low-toxicity. However, developing a method that is fast and green, and have large-scale production of CaCO 3 -based DDS remains a challenge. Here, inspired by biomineralization, for the first time, we develop a one-pot, l -lysine (Lys)-mediated biomineralization method using a CO 2 bubbling procedure to green, simply and quickly prepare CaCO 3 -based DDS. The presence of Lys not only improved the yield of CaCO 3 , but also controled morphology and crystal phase of CaCO 3 . Meanwhile, two different crystal forms of CaCO 3 microspheres were used in the pH-responsive release of cancer drug Sanguinarine (SAN): calcite CaCO 3 (CC) and vaterite CaCO 3 (VC). The structure of the as-prepared CC and VC was characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and Brunauer-Emmett-Teller analysis (BET). The possible formation mechanism was proposed. As a potential DDS, both different DDS showed good drug-loading capacity (CC: 63.5 %; VC: 51.9 %), good biocompatibility, pH-sensitivity and low-toxicity. Meanwhile, after loading the SAN, it had obvious inhibitory effects to cancer cells. However, they presented significant differences in drug loading rate, loading capacity and pH-sensitivity due to differences in crystal form and morphology. This biomineralization method of green synthesis of CaCO 3 -based DDS using CO 2 provided a possibility for industrial application of DDS, and the comparative study of CaCO 3 with different morphologies and crystal forms gave a good idea for the design of DDS.