Functional Hydroxyapatite Nanoparticles for Cancer Treatment

Calcium phosphates, because of their superior biocompatibility, bioactivity and compositionally similar to the mineral phases of the bone, are preferred as bone grafts and tissue engineering. Several phases of calcium phosphate have currently been used in the biomedical field. Among those, HAp, due to the highest stability, is the most popular and well-known phase of calcium phosphate, which is the most stable with the variation of pH, temperature or composition of the physiological fluid. In our preliminary study, we observed crystalline nano-sized HAp could be easily synthesized by wet chemical precipitation in water without addition of any surfactant, showing the particles belonged to biodegradable B type carbonated HAp and could be well-suspended in culture medium for a relatively long period of time, indicating it could be an ideal candidate for biological application. In recent years, cancer treatment has been always a global and imperative health issue. With these encouraging results, in this study, we ask whether functional crystalline HAp can treat cancer, involving (1) Enhancing immune-activation of macrophage by delivering CpG ODN-loaded HAp nanoparticles; (2) Reactive oxygen species (ROS)-enhanced cancer treatment by hafnium-doped HAp nanoparticles with ionizing radiation. In the first part of our study, we synthesized HAp nanoparticles by wet chemical precipitation method. HAp nanoparticles loaded with CpG ODN were characterized for their stability, size, morphology, loading capacity, and cytokine induction behavior. The results revealed TLR9 dependent cytokine (IL-12 and IL-6) was enhanced by loading CpG ODN onto crystalline HAp nanoparticles, indicating HAp facilitated the retaintion of ODNs in endolysosome, giving rise to specific CpG ODN/ TLR9 interactions. The results suggest HAp may be an appropriate vehicle for ODN delivery and cancer immunotherapy. In the second part, 15% of hafnium ions were successfully doped into HAp crystal by wet chemical precipitation method. The human lung epithelia cell line A549 was selected as the in-vitro and in-vivo model. The results suggest Hf4+-doped HAp nanoparticles enhance the quantity of ROS in cells and induce cell apoptosis by bombarding with ionizing radiation, indicating a possible approach instead of photodynamic therapy to treat deeper tumor.