Abstract
Amorphous calcium carbonate (ACC), as a naturally nontoxic biomineral, shows great potential for biomedical applications, with intrinsic advantages of pH-dependent degradability, biocompatibility, simple chemical composition, as well as low cost and ease of large-scale production. However, the major obstacle to develop ACC nanoparticles as a pH-responsive nanomedicine is the high aqueous instability of ACC including its ease of dissolution and phase transition. Herein, an alcoholic suspension of ACC nanoparticles preloaded with doxorubicin (DOX) and indocyanine green (ICG) was obtained using a simple vapor-diffusion process. To preserve their stability while retaining their pH-responsiveness, polypyrrolidone (PVP) and phytic acid (IP6) were introduced to protect the ACC from unexpected crystallization in aqueous environment. The surface of the resulting nanoparticles was further covered with closely packed small Au nanoparticles via hydroxylamine reduction of HAuCl4. The surface coating of Au nanoparticles not only facilitated specific PEGylation through thiol linkages but also the photothermal response in the near-infrared tissue optical window. Overall, a co-drug delivery platform with pH-responsive release capability was successfully established to improve the therapeutic efficacy in tumor cells.