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.
A novel targeting drug delivery system for cancer therapy based on H + -triggered bubble-generating nanosystems (BGNSs) was engineered. First, hollow mesoporous silica nanoparticles (HMSNs) were used to load doxorubicin (DOX). Then, the obtained drug-loaded HMSNs were treated with NaHCO 3 to prepare the BGNSs. The BGNSs were coated with polydopamine (pDA), and finally, folic acids (FA) were anchored on the nanosystems to obtain the desired nanoscale drug delivery system ( [email protected] ). [email protected] was effectively internalized by cancer cells through folate receptor-mediated endocytosis and generated CO 2 bubbles under the acidic environment of the lysosomes, thus enhancing lysosomal membrane permeability (LMP) to release caspase-3 into the cytoplasm, resulting in cancer cell death via an apoptosis-like pathway. Notably, we demonstrated that the [email protected] exhibited a significant simultaneous synergetic cytotoxicity against MCF-7 cells and remarkably overcame the multidrug resistance (MDR) of MCF-7/ADR cells. Moreover, compared to free DOX and a nanosystem without FA modification (BGNSs), the [email protected] induced relatively minor side effects in the MCF-10A cells. Therefore, the results showed that [email protected] , as a targeted drug delivery system, have a good probability of overcoming the MDR of tumor cells with minor side effects on normal cells.
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