Synthesis of Superparamagnetic CaCO3 Mesocrystals for Multistage Delivery in Cancer Therapy

To develop a new system for site-specific targeting, superparamagnetic CaCO3 mesocrystals with the properties of biocompatibility and biodegradability are designed and synthesized. They serve as carriers for the co-delivery of drug and gene nanoparticles via a multistage method for cancer therapy. With a porous structure, the mesocrystalline CaCO3 particles encapsulate doxorubicin (DOX), Au-DNA, and Fe3O4@silica nanoparticles for magnetic control and therapy. As stage 1 microparticles (S1MPs), the nanoparticles-CaCO3 system is designed to protect functional sections from degradation and phagocytosis in blood circulation. After the particle margination in vascular walls, the Au-DNA nanoparticles (stage 2 nanoparticles, S2NPs) and DOX are gradually released from S1MPs by degradation towards targeted tissues for biomedical therapy. The nanoparticles-CaCO3 system exhibits high efficiency of intracellular delivery, especially in nuclear invasion. The successful expression of reporter gene and intracellular transport of DOX in vitro suggest potential as a co-delivery system for drug and gene therapy. In a mouse tumor model, the system with particle margination and two-step strategy affords the protection of functional nanoparticles and drug from clearance and inactivation by enzymes and proteins in vivo. The targeted delivery of S2NPs into tumors by this system is tenfold more efficient than that of the nanoparticles themselves. The drug is observed to be widely distributed in tumor slices. Thus, this platform exhibits an efficient approach in the targeted delivery of therapeutic nanoparticles and molecules via a multistage strategy, and can be used as a potential system in co-delivery of multiple agents for biomedical imaging and therapy.