Hollow mesoporous hydroxyapatite nanoparticles (hmHANPs) with enhanced drug loading and pH-responsive release properties for intracellular drug delivery

Biocompatible and biodegradable hydroxyapatite nanoparticles with a hollow core and mesoporous shell structure (denoted as hmHANPs) are synthesized by an opposite ion core/shell strategy and applied to pH-responsive intracellular drug delivery systems (DDS). The synthesized hmHANPs have several advantages over solid hydroxyapatite nanoparticles (HANPs), where the hollow and mesoporous structure enhances drug-loading capacity, and the thin hydroxyapatite shell structure reduces burst release of drug and provides pH-responsive release. Doxorubicin (DOX), a therapeutic anticancer drug, was loaded in hmHANPs and HANPs for intracellular drug delivery systems (DDS). Compared to HANPs having a low drug-loading efficacy (17.9%), hmHANPs exhibited an excellent drug-loading efficacy (93.7%). In addition, the release amount of DOX from hmHANPs was 2.5-fold the amount from HANPs. Compared with free DOX, the anticancer efficacy of DOX-loaded hmHANPs was greatly enhanced, as evidenced by the results of MTT assays and confocal laser scanning microscopy using breast cancer cells (BT-20). The synthesized hmHANPs show great potential as drug nanovehicles with high biocompatibility, enhanced drug loading, and pH-responsive features for future intracellular DDS.