Constructing H+-triggered bubble generating nano-drug delivery systems using bicarbonate and carbonate

Abstract

Nanoparticles have the great potential to act as drug delivery carriers, and such systems must effectively deliver the drug to the cancer cells, and provide intracellular drug release. In this research, two types of H⁺-triggered bubble generating nanosystems (BGNS) were developed which were obtained using hollow mesoporous silica nanoparticles loaded with doxorubicin and subsequently treated with bubble generating agents, i.e., sodium bicarbonate (SBC) and ammonium carbonate (AC). These were named BGNS-SBC and BGNS-AC. After internalization by the tumor cells, the H⁺ reacts with bicarbonate or carbonate to generate carbon dioxide bubbles quickly in an acidic environment of endo/lysosomes, which results in lysosomal membrane permeabilization (LMP). Then, the enhanced LMP induced cancer cell death by an apoptosis-like pathway because of the release of caspase-3 from the lysosome into the cytoplasm. In addition, BGNS-SBC and BGNS-AC possessed remarkable cytotoxicity against MCF-7 cells and efficiently overcame the multidrug resistance (MDR) of MCF-7/adriamycin cells. Therefore, these bubble generating nanosystems could be a promising nanocarrier for the treatment of tumors.