Hollow Manganese Phosphate Nanoparticles as Smart Multifunctional Probes for Cancer Cell Targeted Magnetic Resonance Imaging and Drug Delivery

Multifunctional probes for simultaneous magnetic resonance imaging (MRI) and drug delivery have attracted considerable interest due to their promising potential applications in the early-stage diagnosis and therapy of the diseases. In this study, hollow manganese phosphate nanoparticles (HMP NPs) with an average diameter of 18 nm were synthesized and aminated through silanization, which enabled the covalent conjugation of biocompatible poly(ethylene glycol) (PEG) on their surfaces. The anti-tumor drug doxorubicin (DOX) could be loaded into the hollow cavities. Under physiological conditions (pH 7.4), the NPs showed low MRI T₁ contrast (r₁ = 1.19 L·mmol^-1·s^-1), whereas high T₁ enhancement (r₁ = 5.22 L·mmol^-1·s^-1) was achieved after dissolving them in endosome/lysosome mimetic conditions (pH 5.4). This is due to the fact that the NPs were easily eroded, which resulted in the release of Mn²⁺ at low pH. To use this interesting phenomenon for targeted DOX drug delivery, we conjugated the tumor-targeting ligand folic acid (FA) on HMP NPs and investigated their drug delivery capacity and cytotoxicity to cell lines expressing different amount of folate receptor (FR). KB cells showed more significant cellular uptake than HeLa cells and A549 cells, as confirmed by confocal laser scanning microscopy (CLSM), flow cytometry and cellular T₁-weighted MRI. Furthermore, the drug-loaded HMP NPs exhibited greater cytotoxicity to KB cells. Our results suggest that functionalized HMP NPs can act as an effective multifunctional probe for selective diagnosis with MRI, as well as giving efficient targeted drug delivery.