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.

Cosynthesis of cargo-loaded hydroxyapatite/alginate core-shell nanoparticles (HAP@Alg) as pH-responsive nanovehicles by a pre-gel method.

A new core-shell nanostructure consisting of inorganic hydroxyapatite (HAP) nanoparticles as the core and organic alginate as the shell (denoted as HAP@Alg) was successfully synthesized by a pre-gel method and applied to pH-responsive drug delivery systems (DDS). HAP@Alg nanoparticles have the advantages of hydroxyapatite and alginate, where hydroxyapatite provides pH-responsive degradability, and alginate provides excellent biocompatibility and COOH functionality. Through the subsequent addition of CaCl(2) and phosphate solutions to the alginate solution, HAP@Alg nanoparticles with controllable particle sizes (ranging from 160 to 650 nm) were obtained, and their core-shell structure was confirmed through transmission electron microscopy (TEM) observation. Rhodamine 6G (R6G), a positively charged dye, was selected as a model drug for pH-sensitive DDS. R6G was encapsulated in the HAP/Alg nanoparticles upon synthesis, and its loading efficiency could reach up to approximately 63.0%. The in vitro release behavior of the loaded R6G at different pH values was systematically studied, and the results indicated that more R6G molecules were released at lower pH conditions. For example, after releasing for 8 h, the release amount of R6G at pH 2.0 was 2.53-fold the amount at pH 7.4. We attributed this pH-sensitive release behavior to the dissolution of the HAP core in acidic conditions. The results of the MTT assay and confocal laser scanning microscopy indicated that the HAP@Alg were successfully uptaken by liver cancer cells (HepG2) without apparent cytotoxicity. The synthesized HAP@Alg nanoparticles show great potential as drug nanovehicles with high biocompatibility, enhanced drug loading, and pH-responsive features for future intracellular DDS.

Biocompatible, surface functionalized mesoporous titania nanoparticles for intracellular imaging and anticancer drug delivery.

Mesoporous titania nanoparticles (MTNs) with excellent biocompatibility (LC(50)≈ 400 µg mL(-1)) and a large surface area (ca. 237.3 m(2) g(-1)) were synthesized and further functionalized with a phosphate-containing fluorescent molecule (i.e. flavin mononucleotide; FMN) and loaded with an anticancer drug (i.e. Doxorubicin) for successful intracellular bioimaging and drug delivery, respectively, in human breast cancer cells BT-20.