A Logic AND-Gated Sonogene Nanosystem for Precisely Regulating the Apoptosis of Tumor Cells

To date, many methods have been developed for inducing tumor cell death, such as using chemical drugs and radiation. However, all of them have a common problem, a lack of mechanisms for precisely regulating the death of tumor cells. It often leads to nonspecific death and systemic side effects. Therefore, the efficacy and further application of these traditional methods are limited. In this paper, a logic AND-gated sonogene nanosystem was designed for precisely regulating the apoptosis of tumor cells. The running of this system required two essential parts, MscL I92L channel protein and ultrasound. Ultrasound could open the MscL I92L protein channel which when expressed on cells triggers the influx and outflux of small molecules through the channel. When the channel is kept open for a long time, Ca²⁺ influx becomes excessive which in turn activates the Ca²⁺ apoptosis pathway of cells. The expression of MscL I92L protein and the applying of ultrasound constituted the logic AND gate which could implement the precise regulation to apoptosis. This strategy would help reduce nonspecific triggers and side effects. In this system, cationic nanoliposomes were prepared as the carrier for effectively delivering MscL I92L plasmids to tumor cells in vivo. We investigated the apoptosis-promoting effect of this system in different tumor cell lines (HeLa, B16, and 4T1). The results demonstrated that the apoptosis rate was highest in the B16 cell line (the early apoptosis rate was 11.9% and the late apoptosis rate was 59.1%) when the cells were subjected to consistent ultrasound (6 MHz, 15 W) for 30 min. This logic AND-gated sonogene nanosystem is expected to provide a new strategy and development direction for tumor therapy.