Microbubble-based liposomal delivery of dasatinib and COL11A1siRNA for enhanced combination therapy against lung adenocarcinoma

Abstract

Current chemotherapeutic treatments have severely limited effectiveness against tumors. Co-delivery of chemotherapeutic drugs and small interfering RNA (siRNA) in a nanoliposomal drug delivery system is known to selectively improve cytotoxicity against tumors. The current study aimed to achieve augmented combination therapy (Dasatinib-DST and siRNA targeting COL11A1 gene) against lung adenocarcinoma (LUAD) in vitro. The microbubble liposome (MB-LP)-based codelivery system (DST and COL11A1) used in this study was prepared using the thin film hydration method. The resulting codelivery system (MB-LP/DST/siRNA) average size and zeta potential were about 1611.5 nm and − 10.35 mV, respectively. Nevertheless, the average size of the MB-LP drug delivery system alone was 530 nm. The percentage encapsulation efficiency (% EE) of the combination drug (DST and COL11A1^siRNA) in the MB-LP nanodelivery system was 62.9%. The surface morphology of the codelivery system (MB-LP/DST/siRNA) was analysed using a High-Resolution Scanning Electron Microscope (HR-SEM) and a High-Resolution Transmission Electron Microscopy (HR-TEM). Both confirmed the spherical shape of the MB-LP system. MTT-based proliferation analysis in vitro revealed that DST and COL11A1^siRNA containing MB-LP codelivery system caused significant inhibition of cell proliferation against LUAD. This is the first study that suggests the co-delivery of the chemotherapeutic drug (DST) and COL11A1^siRNA using the MB-LP drug delivery system facilitates an anti-proliferative effect against LUAD cells. Additionally, we also conclude that these prospective results strengthen the evidence on the potential of combination therapy (DST and COL11A1^siRNA) against LUAD.