Metal-polyphenol network coated magnetic hydroxyapatite for pH-activated MR imaging and drug delivery

Engineered nanoparticles responsive to tumor microenvironment parameters such as pH have been developed as drug carriers and for magnetic resonance imaging (MRI) as contrast agents (CA). Nanoscale hydroxyapatite (HAP) has good biocompatibility and specific inhibition of tumor cells. However, the inherent tendency of nanoscale HAP to agglomerate and degrade under natural conditions has hindered its further application. To address this challenge, polyacrylic acid-coordinated Mn²⁺ and F^- co-doped nanoscale HAP (Mn_xFHA-PAA) were developed for MRI and doxorubicin (DOX) loading. Moreover, the metal-polyphenol network (MPN) formed by ligating tannic acid (TA) and Fe³⁺ was successfully functionalized onto the surface of Mn_xFHA-PAA-DOX. The pH-sensitive MPN improves biocompatibility and therapeutic efficacy while preventing the premature release of DOX in a neutral environment. It was demonstrated that the mesoporous structure of Mn_xFHA-PAA@TA-Fe nanoparticles with good dispersion, high specific surface area and large pore size, which can reach more than 90 % encapsulation efficiency (EE) for DOX. Mn_xFHA-PAA-DOX@TA-Fe degrades at low pH and releases Mn²⁺ and DOX that are confined in the nanoparticles. Binding of Mn²⁺ to proteins leads to increased relaxation and enhanced MRI contrast. Such nanoparticles with sensitive pH responsiveness have great potential for tumor diagnosis and therapeutic synergy.