A pH-sensitive carrier based-on modified hollow mesoporous carbon nanospheres with calcium-latched gate for drug delivery

A novel nanocarrier based-on hollow mesoporous carbon nanospheres (HMCNs) with primary amines on its surface, a large cavity, and good hydrophilicity was synthesized by a hydrothermal reaction. The primary amine functionalities on the mesoporous carbon were used as the initiation sites for growing poly (epichlorohydrin) (PCH) chains. The chlorine groups in the side chain of PCH were replaced with imidazole as the pendant groups. Calcium chloride (CaCl₂) was applied as a capping agent. The coordination bonding was formed between pendant imidazole groups and calcium ions. Doxorubicin (DOX) was selected as a model of hydrophilic anticancer drug and was loaded onto the nanocarrier and released through the cleavage of the pH-sensitive coordination bonding. The gating mechanism enables the nanocarrier to store and release the calcium ions and the DOX molecules trapped in the pores. MTT assay toward HeLa cells indicated that the nanocarrier had low toxicity because of the surface modification with the oxygen-rich polymer. The cellular uptake of the pH-sensitive nanocarrier for HeLa cancer cell lines was confirmed by CLSM images and flow cytometry. So, the novel pH-sensitive nanocarrier can be applicable to carry and release both DOX drug and calcium ions for cancer treatment.