Survivin has been shown to be widely expressed in most tumor cells, including lung and breast cancers. Due to limited siRNA delivery, it is more challenging to target survivin using knockdown‐based techniques. Designing and developing new, bifunctional chemical molecules with both selective anti‐proliferative activity and effective siRNA transfection capabilities by targeting a particular gene is important to treat aggressive tumors like triple‐negative breast tumors (TNBC). The cationic lipids deliver small interfering RNA (siRNA) and also display inherent anti‐cancer activities; therefore, cationic lipid therapies have become very popular for treating malignant cancers. In the current study, we attempted to synthesize a series of acid‐containing cationic lipids, anthranilic acid‐containing mef lipids, and indoleacetic acid‐containing etodo lipids etc. Further, we elucidated their bi‐functional activity for their anticancer activity and survivin siRNA‐mediated anti‐cancer activity. Our results showed that lipoplexes with siRNA‐Etodo: Dotap (ED) and siRNA‐Mef: Dotap (MD) exhibited homogeneous particle size and positive zeta potential. Further, biological investigations resulted in enhanced survivin siRNA delivery with high stability, improved transfection efficiency, and anti‐cancer activity. Additionally, our findings showed that survivin siRNA lipoplexes (ED and MD) in A549 cells and 4T1 cells exhibited stronger survivin knockdown, enhanced apoptosis, and G1 or G2/M phase arrest in both cell types. In vivo results revealed that treatment with survivin complexed lipoplexes significantly reduced tumor growth and tumor weight compared to control. Thus, our novel quaternary amine‐based liposome formulations are predicted to open up new possibilities in the development of a simple and widely utilized platform for siRNA delivery and anti‐cancer activities.

Survivin has been reported to be expressed abundantly in most of the tumor cells including lung cancer and breast cancers. To combat aggressive cancers like triple-negative breast cancer (TNBC) it is necessary to design and develop a new, bifunctional chemical with both selective anti-proliferative activity and siRNA transfection capabilities by targeting a specific gene. The cationic lipids deliver small interfering RNA (siRNA) and also display inherent anti-cancer activities; therefore, the cationic lipid therapies have become very popular for treating malignant cancers. In the current study, we made an attempt to synthesize a series of acid-containing cationic lipids, anthranilic acid-containing mefenamic lipid and indoleacetic acid-containing etodolac lipids, and elucidated their bi-functional activity for selective anticancer activity and survivin siRNA mediated anti-cancer activity. Our results, showed that, lipoplexes with siRNA-Etodo:Dotap (ED) and siRNA-Mef:Dotap (MD) exhibited homogeneous particle size and positive zeta potential. Further, biological investigations resulted in enhanced survivin siRNA delivery with high stability, improved transfection efficiency, and efficacy. Additionally, our findings showed that survivin siRNA lipoplexes (ED and MD) in A549 cells and 4T1 cells exhibited stronger survivin knockdown, enhanced apoptosis, and G2/M phase arrest in both the cell types. In vivo results revealed that, treatment with survivin complexed lipoplexes showed significant reduction of tumour growth and tumour weight compared to control. Thus, our novel quaternary amine-based liposomes formulations are predicted to open up new possibilities in the development of a simple and widely utilized platform for siRNA delivery and anti-cancer activities.