Nanobubble-mediated co-delivery of siTRIM37 and IR780 for gene and sonodynamic combination therapy against triple negative breast cancer.

Abstract

Gene therapy often fails due to enzyme degradation and low transfection efficiency, and single gene therapy usually cannot completely kill tumor cells. Several studies have reported that tripartite motif-containing protein 37 (TRIM37) plays a significant role in promoting the occurrence and development of triple negative breast cancer (TNBC). Herein, we constructed siTRIM37 and IR780 co-loaded nanobubbles (NBs) to achieve the combination of gene therapy and sonodynamic therapy (SDT) against TNBC. On the one hand, ultrasound irradiation causes siRNA@IR780 NBs rupture to produce ultrasound targeted NB destruction effect, which promotes the entry of IR780 and siTRIM37 into cells, increasing the local concentration of IR780 and gene transfection efficiency. On the other hand, under the stimulation of ultrasound, IR780 generates reactive oxygen species to kill TNBC cells. Mechanism studies reveal that TRIM37 is an anti-apoptotic gene in TNBC, and inhibiting TRIM37 expression can induce cell death through the apoptotic pathway. And the combination of siTRIM37 and SDT can aggravate the degree of apoptosis to increase cell death. Therefore, siRNA@IR780 NBs-mediated combination therapy may provide a new treatment approach for TNBC in the future.