Surface grafting of rare-earth ions doped hydroxyapatite nanorods (HAp:Ln(Eu/Tb)) with hydrophilic copolymers based on ligand exchange reaction: Biological imaging and cancer treatment

Rare-earth ions doped hydroxyapatite nanoparticles (HAp:Ln NPs) have demonstrated to be very promising candidates for biological imaging applications owing to their small size and chemical compositions similar to bone. However, these HAp:Ln NPs with controllable size and morphology should be prepared under hydrothermal treatment with hydrophobic molecules as the protective layers. The hydrophobic nature of these luminescent HAp:Ln NPs largely impeded their applications in biomedical fields. In this study, a novel and effective strategy has been developed for the surface modification of HAp:Ln nanorods through the combination of surface ligand exchange reaction and reversible-addition fragmentation chain transfer (RAFT) polymerization using 2-methacryloyloxyethyl phosphorylcholine (MPC) and itaconic acid (IA) as the monomers. Herein, a small molecule adenosine 5′-monophosphate disodium salt (AMP) that contains a phosphate group and two hydroxyl groups was used to displace the hydrophobic oleic acid on pristine HAp NPs through surface ligand exchange reaction owing to its stronger interaction with HAp NPs. On the other hand, the MPC and IA were introduced on HAp NPs through RAFT polymerization after the chain transfer agent was immobilized on the HAp NPs through the esterification reaction. The poly(IA-MPC) could not only endow the high water dispersibility but also be used for loading anticancer agent cisplatin (CDDP) through coordination interaction. To evaluate their potential biomedical applications, the cell uptake behavior, drug loading capacity and release behavior as well as cell viability of HAp:Ln-AMP-poly(IA-MPC) polymeric composites were examined. We demonstrated that the method developed in this work is very effective for introduction of functional polymers onto HAp:Ln nanorods. The HAp:Ln-AMP-poly(IA-MPC) composites are promising for cell imaging and controlled delivery of CDDP.