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Published on: June 13, 2014
Targeted therapy of angiogenesis using anti-VEGFR2 and anti-NRP-1 nanobodies
Elmira Karami1, Shamsi Naderi1, Reyhaneh Roshan1
1Venom and Biotherapeutics Molecules Laboratory, Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
Purpose:
Targeted therapy in cancer researches is a promising approach that can resolve drawbacks of systematic therapeutics. Nanobodies are potent therapeutics due to their high specificity and affinity to the target.
Methods:
In this study, we evaluated the effect of the combination of anti-vascular endothelial growth factor receptor 2 (anti-VEGFR2) and anti-neuropilin-1 (anti-NRP1) nanobodies both in vitro (MTT, and tube formation assay) and in vivo (chick chorioallantoic membrane (CAM), and Nude mice treatment assay).
Results:
Our results showed that the combination of two nanobodies (anti-VEGFR2/NRP-1 nanobodies) significantly inhibited proliferation as well as tube formation of human endothelial cells effective than a single nanobody. In addition, the mixture of both nanobodies inhibited vascularization of chick chorioallantoic membrane ex ovo CAM assay as compared to a single nanobody. Moreover, the mixture of both nanobodies significantly inhibited tumor growth of the mice (tumor volume and weight) higher than individual nanobodies (P < 0.05).
Conclusion:
Our results offer a promising role of combination therapies in cancer therapy as well as angiogenesis.
Insights
Combination nanobodies targeting VEGFR2 and NRP1 show enhanced anti-cancer effects. This dual-targeted therapy significantly inhibits tumor growth and angiogenesis more effectively than single nanobodies.
Area of Science:
- Oncology
- Nanotechnology
- Molecular Biology
Background:
- Targeted cancer therapies offer advantages over systemic treatments.
- Nanobodies are highly specific and affinity-based therapeutic agents.
Purpose of the Study:
- To evaluate the combined efficacy of anti-VEGFR2 and anti-NRP1 nanobodies.
- To compare the dual-nanobody therapy against single-nanobody treatments in vitro and in vivo.
Main Methods:
- In vitro assays: MTT for proliferation, tube formation assay.
- In vivo assays: Chick chorioallantoic membrane (CAM) vascularization, Nude mice tumor growth inhibition.
Main Results:
- Combined anti-VEGFR2/NRP-1 nanobodies significantly inhibited endothelial cell proliferation and tube formation.
- The nanobody mixture demonstrated superior inhibition of CAM vascularization compared to single nanobodies.
- Dual-nanobody therapy significantly reduced tumor volume and weight in mice (P < 0.05).
Conclusions:
- Combination nanobody therapy holds promise for cancer treatment.
- Dual targeting of VEGFR2 and NRP1 enhances anti-angiogenic and anti-tumor effects.
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