Biomimetic hollow mesoporous hydroxyapatite microsphere with controlled morphology, entrapment efficiency and degradability for cancer therapy

Abstract

Hollow hydroxyapatite (HAp) microspheres bearing hierarchical structures have been one of the most popular carriers for drug delivery. However, it's been challenging to find an approach that can simultaneously control the morphology, degradability and drug loading/releasing properties of the microsphere. In this study, hollow mesoporous microspheres composed of nano-sized HAp crystals were hydrothermally synthesized from hollow CaCO₃ precursors prepared via sodium dodecyl sulfate (SDS)-assisted precipitation. The particle size, hollow structure and wall thickness of the fabricated hollow mesoporous carbonated HAp microsphere (CHAM) could be facilely regulated by tailoring the concentration of SDS in the reaction. The achieved carbonate-containing CHAMs were demonstrated to be suitable for drug delivery through either surface attachment or intracellular engulfment without causing cytotoxicity. In addition, their distinguished biodegradability and sustained drug release properties in a pH-dependent manner might allow them to be used in cancer treatment by targeting the acidic microenvironment in a solid tumor. Moreover, the CHAM prepared using SDS at its critical micelle concentration (CMC) was suggested to be optimal for anti-cancer therapy due to its highest entrapment efficiency of cis-diammineplatinum(II) dichloride (CDDP) and the strongest killing effect on human squamous cell carcinoma in vitro.