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

Abstract

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 NaHCO3 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 (BGNSs@pDA-FA). BGNSs@pDA-FA was effectively internalized by cancer cells through folate receptor-mediated endocytosis and generated CO2 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 BGNSs@pDA-FA 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 BGNSs@pDA-FA induced relatively minor side effects in the MCF-10A cells. Therefore, the results showed that BGNSs@pDA-FA, as a targeted drug delivery system, have a good probability of overcoming the MDR of tumor cells with minor side effects on normal cells.