Cationic liposomes co-deliver chemotherapeutics and siRNA for the treatment of breast cancer

Li, Mingyuan; Li, Shuangshuang; Li, Yuan; Yang, Guang; Xie, Yanbo; Su, Wenyu; Wu, Jianru; Jia, Lin; Ma, Wenlin; Li, Haiming; Guo, Na; Yu, Peng

doi:10.1016/j.ejmech.2022.114198

Cited by 33 publications

(17 citation statements)

References 43 publications

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“…Thereafter, the flask was kept at room temperature overnight to hydrate the lipid components. In the end, bath sonication was performed to reduce the size of the liposome [25].…”

Section: Lipid Film Hydration Methods For Liposome Formationmentioning

confidence: 99%

“…Mouse TNBC cell line, 4T1 cells (0.5 × 10 6 ) were injected into the 4 th inguinal mammary gland of the mouse (6-8 weeks old) to develop an orthotopic tumor model. After tumors attain 100-200 mm 3 , mice were randomized (n=6) into different (7) groups (ED lipoplexes-2 mg/kg, ED lipoplexes-1 mg/kg, EDL Liposome-2 mg/kg, MD lipoplexes -1.5 mg/kg, MD lipoplexes-0.75 mg/kg, MDLliposome-1.5 mg/kg, and Control-Normal saline). MD and ED groups' 0.5 mg/kg survivin siRNA-containing liposome and liposome alone (EDL and MDL) were administered to the treatment group intravenously and the treatment was given weekly twice for a period of 25 days and tumor sizes were measured and the tumor volumes were calculated (mm3).…”

Section: Orthotopic Model Using Tnbc Cellsmentioning

confidence: 99%

“…Chemotherapeutic agents cause substantial harm to healthy cells in addition to being exceedingly toxic to cancer cells. The main theoretical and practical problem with cancer treatment is non-specific targets in humans by chemotherapeutic drugs [7]. Given that a single pharmacological therapy can occasionally be unsuccessful, combining at least two distinct therapeutic methods is also becoming more and more frequent for the treatment of cancer.…”

Section: Introductionmentioning

confidence: 99%

“…Cationic liposomes form complexes with negatively charged siRNA and offers better transfection efficiency with minimal immunogenicity, toxicity, and degradability [23,24]. Delivering the siRNA by employing cationic liposomes to transport siRNA may be able to address issues with siRNA's short half-life, low serum stability, and quick nuclease destruction [25]. In this study, intensive efforts have been made to produce safe and effective gene delivery agents that give high transfection efficiency and deliver at the intended site of the action.…”

Section: Introductionmentioning

confidence: 99%

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Abrogation of the triple-negative breast tumor growth in orthotopic mouse models through survivin silencing using liposome-mediated delivery of siRNA

Vaidya

Mohod

Chowdary

et al. 2022

Preprint

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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.

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“…Thereafter, the flask was kept at room temperature overnight to hydrate the lipid components. In the end, bath sonication was performed to reduce the size of the liposome [25].…”

Section: Lipid Film Hydration Methods For Liposome Formationmentioning

confidence: 99%

Section: Orthotopic Model Using Tnbc Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Abrogation of the triple-negative breast tumor growth in orthotopic mouse models through survivin silencing using liposome-mediated delivery of siRNA

Vaidya

Mohod

Chowdary

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…To maximize the loading rate of siRNA and improve the stability of blood circulation, positively charged cationic liposomes were developed [ 92 , 93 ]. It has been proven that cationic liposomes are the most promising siRNA carriers with high load rates, biocompatibility, and biodegradability.…”

Section: Sirna Nanocarriersmentioning

confidence: 99%

Research Status and Prospect of Non-Viral Vectors Based on siRNA: A Review

Tong

Liu

Cao

et al. 2023

IJMS

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Gene therapy has attracted much attention because of its unique mechanism of action, non-toxicity, and good tolerance, which can kill cancer cells without damaging healthy tissues. siRNA-based gene therapy can downregulate, enhance, or correct gene expression by introducing some nucleic acid into patient tissues. Routine treatment of hemophilia requires frequent intravenous injections of missing clotting protein. The high cost of combined therapy causes most patients to lack the best treatment resources. siRNA therapy has the potential of lasting treatment and even curing diseases. Compared with traditional surgery and chemotherapy, siRNA has fewer side effects and less damage to normal cells. The available therapies for degenerative diseases can only alleviate the symptoms of patients, while siRNA therapy drugs can upregulate gene expression, modify epigenetic changes, and stop the disease. In addition, siRNA also plays an important role in cardiovascular diseases, gastrointestinal diseases, and hepatitis B. However, free siRNA is easily degraded by nuclease and has a short half-life in the blood. Research has found that siRNA can be delivered to specific cells through appropriate vector selection and design to improve the therapeutic effect. The application of viral vectors is limited because of their high immunogenicity and low capacity, while non-viral vectors are widely used because of their low immunogenicity, low production cost, and high safety. This paper reviews the common non-viral vectors in recent years and introduces their advantages and disadvantages, as well as the latest application examples.

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Synthesis and Characterization of a New Cationic Lipid: Efficient siRNA Delivery and Anticancer Activity of Survivin‐siRNA Lipoplexes for the Treatment of Lung and Breast Cancers**

et al. 2023

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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.

show abstract

Cationic liposomes co-deliver chemotherapeutics and siRNA for the treatment of breast cancer

Cited by 33 publications

References 43 publications

Abrogation of the triple-negative breast tumor growth in orthotopic mouse models through survivin silencing using liposome-mediated delivery of siRNA

Abrogation of the triple-negative breast tumor growth in orthotopic mouse models through survivin silencing using liposome-mediated delivery of siRNA

Research Status and Prospect of Non-Viral Vectors Based on siRNA: A Review

Synthesis and Characterization of a New Cationic Lipid: Efficient siRNA Delivery and Anticancer Activity of Survivin‐siRNA Lipoplexes for the Treatment of Lung and Breast Cancers**

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