Highly penetrating nanobubble polymer enhances LINC00511-siRNA delivery for improving the chemosensitivity of triple-negative breast cancer.

Abstract

Ultrasound-mediated nanobubble destruction (UMND), which can utilize the physical energy of ultrasound irradiation to improve the transfer efficiency to target cells is becoming one of the most promising carriers for gene delivery. The purpose of this study was to establish cell-penetrating peptide (CPP)-loaded nanobubbles (CNBs) connected with long intergenic nonprotein coding RNA 00511-small interfering RNA (LINC00511-siRNA) and evaluate its feasibility for improving the chemosensitivity of triple-negative breast cancer in vitro. First, fluorescence imaging confirmed the loading of siLINC00511 on CNBs, and the CNBs-siLINC00511 were characterized by the Zetasizer Nano ZS90 analyzer and transmission electron microscopy. Next, cell counting kit 8 assay was used to detect the inhibitory activity of cisplatin on the proliferation of MDA-MB-231 cells, and the 50% inhibition concentration value before and after transfer was calculated. Finally, the silencing effect of siLINC00511 was evaluated in vitro using an apoptosis assay, transwell assay, real time-PCR and western blotting. UMND combined with CNBs could effectively transfer the siRNA to MDA-MB-231 cells, thus evidently reducing the expression of LINC00511. Furthermore, inhibitory activity of cisplatin on MDA-MB-231 cells was enhanced after downregulation of LINC00511 expression. Downregulation of LINC00511 alters expression of cell cycle-related (CDK 6) and apoptosis-related (Bcl-2 and Bax) proteins in MDA-MB-231 cells. These results suggested that siRNA-CNBs may be an ideal vector for the treatment of tumors, with high efficiency RNA interference under the combined action of UMND. It may provide a new therapeutic method for triple negative breast cancer.