Targeted H+-Triggered Bubble-Generating Nanosystems for Effective Therapy in Cancer Cells

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.