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Control of solid tumor growth in mice using EGF receptor-targeted RNA replicase-based plasmid DNA
B Leticia Rodriguez1, Xinran Li, Kaoru Kiguchi
1College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA.
Aim:
Previously, it was shown that treatment of tumor-bearing mice with an RNA replicase-based plasmid that produces dsRNA when transfected into tumor cells significantly inhibited the tumor growth. In the present study, the feasibility of further improving the anti-tumor activity of the RNA replicase-based plasmid by targeting it into tumors cells was evaluated.
Material & Methods:
An EGF-conjugated, polyethylene glycosylated cationic liposome was developed to deliver the RNA replicase-based plasmid, pSIN-β, into EGF receptor-overexpressing human breast cancer cells (MDA-MB-468) in vitro and in vivo.
Results:
Delivery of pSIN-β using the EGF receptor-targeted liposome more effectively controlled the growth of MDA-MB-468 tumors (and human epidermoid carcinoma A431 tumors) in mice than using untargeted liposome. The pSIN-β carried by the EGF receptor-targeted liposome caused the complete regression of MDA-MB-468 tumors in mice, probably due to the enhancement of its proapoptotic, antiproliferative and antiangiogenic activities.
Discussion:
Tumor-targeted RNA replicase-based plasmids hold a strong potential in tumor therapy.
Insights
Targeting RNA replicase-based plasmids to tumor cells using EGF receptor-targeted liposomes significantly enhanced anti-tumor activity. This approach led to complete tumor regression in mice, showing promise for novel cancer therapies.
Area of Science:
- Molecular Biology
- Cancer Research
- Drug Delivery Systems
Background:
- RNA replicase-based plasmids producing dsRNA inhibit tumor growth.
- Targeting therapeutic agents to tumor cells can enhance efficacy.
Purpose of the Study:
- To evaluate the improved anti-tumor activity of an RNA replicase-based plasmid by targeting it to tumor cells.
- To assess the feasibility of using EGF receptor-targeted liposomes for delivering the plasmid.
Main Methods:
- Developed an EGF-conjugated, polyethylene glycosylated cationic liposome.
- Delivered the RNA replicase-based plasmid (pSIN-β) into EGF receptor-overexpressing breast cancer cells (MDA-MB-468) in vitro and in vivo.
Main Results:
- EGF receptor-targeted liposome delivery of pSIN-β was more effective in controlling tumor growth than untargeted liposomes.
- Complete regression of MDA-MB-468 tumors was observed with targeted liposome delivery, likely due to enhanced proapoptotic, antiproliferative, and antiangiogenic activities.
Conclusions:
- Tumor-targeted RNA replicase-based plasmids demonstrate significant potential as a therapeutic strategy for cancer treatment.
- EGF receptor-targeted delivery enhances the anti-tumor efficacy of RNA replicase-based plasmids.
