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

Abstract

Calcium carbonate (CaCO3) 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 CaCO3-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 CO2 bubbling procedure to green, simply and quickly prepare CaCO3-based DDS. The presence of Lys not only improved the yield of CaCO3, but also controled morphology and crystal phase of CaCO3. Meanwhile, two different crystal forms of CaCO3 microspheres were used in the pH-responsive release of cancer drug Sanguinarine (SAN): calcite CaCO3 (CC) and vaterite CaCO3 (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 CaCO3-based DDS using CO2 provided a possibility for industrial application of DDS, and the comparative study of CaCO3 with different morphologies and crystal forms gave a good idea for the design of DDS.