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Published on: June 13, 2014
λ Phage nanobioparticle expressing apoptin efficiently suppress human breast carcinoma tumor growth in vivo
Alireza Shoae-Hassani1, Peyman Keyhanvar, Alexander Marcus Seifalian
1Applied Cell Sciences Department, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran ; Research Center for Science and Technology in Medicine (RCSTiM), Tehran University of Medical Sciences (TUMS), Tehran, Iran.
Abstract:
Using phages is a novel field of cancer therapy and phage nanobioparticles (NBPs) such as λ phage could be modified to deliver and express genetic cassettes into eukaryotic cells safely in contrast with animal viruses. Apoptin, a protein from chicken anemia virus (CAV) has the ability to specifically induce apoptosis only in carcinoma cells. We presented a safe method of breast tumor therapy via the apoptin expressing λ NBPs. Here, we constructed a λ ZAP-CMV-apoptin recombinant NBP and investigated the effectiveness of its apoptotic activity on BT-474, MDA-MB-361, SKBR-3, UACC-812 and ZR-75 cell lines that over-expressing her-2 marker. Apoptosis was evaluated via annexin-V fluorescent iso-thiocyanate/propidium iodide staining, flow-cytometric method and TUNEL assay. Transfection with NBPs carrying λ ZAP-CMV-apoptin significantly inhibited growth of all the breast carcinoma cell lines in vitro. Also nude mice model implanted BT-474 human breast tumor was successfully responded to the systemic and local injection of untargeted recombinant λ NBPs. The results presented here reveal important features of recombinant λ nanobioparticles to serve as safe delivery and expression platform for human cancer therapy.
Insights
Engineered phage nanobioparticles (NBPs) carrying the apoptin gene effectively target and induce apoptosis in breast cancer cells. This novel phage therapy approach shows promise for safe and effective cancer treatment in vitro and in vivo.
Area of Science:
- Oncology
- Nanotechnology
- Virology
Background:
- Phage nanobioparticles (NBPs) offer a novel platform for cancer therapy, potentially overcoming limitations of viral vectors.
- Apoptin, a protein from chicken anemia virus (CAV), selectively induces apoptosis in carcinoma cells.
Purpose of the Study:
- To construct and evaluate a recombinant λ phage NBP expressing apoptin for breast cancer therapy.
- To assess the efficacy of λ ZAP-CMV-apoptin NBPs against HER2-overexpressing breast cancer cell lines and in a mouse model.
Main Methods:
- Construction of a λ ZAP-CMV-apoptin recombinant NBP.
- In vitro apoptosis assays (annexin-V/propidium iodide staining, flow cytometry, TUNEL assay) on BT-474, MDA-MB-361, SKBR-3, UACC-812, and ZR-75 cell lines.
- In vivo study using a nude mouse model with BT-474 human breast tumor xenografts.
Main Results:
- Transfection with λ ZAP-CMV-apoptin NBPs significantly inhibited the growth of all tested breast carcinoma cell lines.
- Systemic and local injection of the recombinant NBPs demonstrated a positive therapeutic response in the BT-474 tumor-bearing mouse model.
Conclusions:
- Recombinant λ nanobioparticles serve as a safe and effective delivery platform for apoptin.
- This phage-based nanobioparticle system holds significant potential for human cancer therapy, particularly for breast tumors.
