Imaging of cationic multifunctional liposome-mediated delivery of COX-2 siRNA
M Mikhaylova1, I Stasinopoulos, Y Kato
1JHU ICMIC Program, The Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Abstract:
Liposomes are a useful means of delivering molecular targeting agents such as small interfering RNA (siRNA) to downregulate specific pathways important in cancer growth and progression. The ability to non-invasively image these carriers is important to ascertain their delivery within the tumor. As cyclooxygenase-2 (COX-2) is an important therapeutic target in cancer, we investigated loading COX-2-specific siRNA into cationic liposomes containing MR contrast agents for imaging delivery in cancer cells and tumors. COX-2 and GAPDH siRNA, as well as Magnevist or Feridex, were loaded directly into the liposomes. These lipoplexes were used for cell transfection of the poorly differentiated and highly metastatic breast cancer cell line MDA-MB-231. PEGylated liposomes loaded with Feridex and fluorescently labeled COX-2 siRNA were used for in vivo delivery of lipoplexes in MDA-MB-231 breast cancer xenografts in female SCID mice. Transient transfection assays demonstrated potent and specific downregulation of the COX-2 protein in cells in culture. Tail vein injections of PEGylated COX-2 lipoplexes resulted in intratumoral delivery of siRNA. Biodistribution studies showed significant localization in the lung, liver and kidney at 24 h. These data demonstrate the feasibility of liposomal-mediated delivery of COX-2-specific siRNA to downregulate COX-2 in cancer cells, and multi-modality imaging of the delivery of specific siRNA in tumors.
Insights
Liposomes effectively deliver cyclooxygenase-2 (COX-2) specific small interfering RNA (siRNA) to cancer cells. This method allows for non-invasive imaging of siRNA delivery, showing potential for targeted cancer therapy.
Area of Science:
- Biomedical Engineering
- Molecular Biology
- Nanotechnology
Background:
- Liposomes are crucial for delivering molecular targeting agents like small interfering RNA (siRNA) to regulate cancer pathways.
- Non-invasive imaging of liposome delivery is essential for confirming tumor targeting.
- Cyclooxygenase-2 (COX-2) is a significant therapeutic target in cancer treatment.
Purpose of the Study:
- To investigate the loading of COX-2 specific siRNA into cationic liposomes with MR contrast agents.
- To enable imaging of liposome delivery in cancer cells and tumors.
- To assess the feasibility of liposomal delivery and imaging for COX-2 targeted cancer therapy.
Main Methods:
- COX-2 and GAPDH siRNA were loaded into liposomes with MR contrast agents (Magnevist or Feridex).
- Lipoplexes were used for cell transfection in MDA-MB-231 breast cancer cells.
- PEGylated liposomes with Feridex and fluorescent COX-2 siRNA were used for in vivo studies in mice xenografts.
Main Results:
- Transient transfection assays confirmed potent and specific downregulation of COX-2 protein in cultured cells.
- Intratumoral delivery of siRNA was achieved via tail vein injection of PEGylated COX-2 lipoplexes.
- Biodistribution studies indicated significant localization in the lung, liver, and kidney within 24 hours.
Conclusions:
- Liposome-mediated delivery of COX-2 specific siRNA is feasible for downregulating COX-2 in cancer cells.
- Multi-modality imaging can track the delivery of specific siRNA within tumors.
- This approach holds promise for targeted cancer treatment and monitoring.
