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A novel peptide specifically targeting ovarian cancer identified by in vivo phage display
Chuying Ma1, Guangfu Yin, Danhong Yan
1College of Materials Science and Engineering, Sichuan University, Chengdu, 610065, China.
Abstract:
Discovery of peptide ligands that can target human ovarian cancer and deliver chemotherapeutics offers new opportunity for cancer therapy. The advent of phage-displayed peptide library facilitated the screening of such peptides. In vivo screening that set in a microanatomic and functional context was applied in our study, and a novel peptide WSGPGVWGASVK targeting ovarian cancer was isolated. The phage clone PC3-1 displaying peptide WSGPGVWGASVK can gain effective access to accumulate in the tumor sites after intravenous injection while reducing its accumulation in normal organs. Positive immunostaining of PC3-1 was located in both sites of tumor cells and tumor blood vessels, which resulted in a diffuse binding pattern through the tumor. In vitro study results confirmed the capability of peptide WSGPGVWGASVK binding to and being internalized by both tumor cells and angiogenic endothelial cells. Flow cytometry analysis revealed that the peptide bound to SKOV3 cells with Kd value of 5.43 ± 0.4 μM. Taken together, it suggested that peptide WSGPGVWGASVK is a lead candidate for delivering therapeutics to penetrate into tumors.
Insights
Researchers discovered a novel peptide, WSGPGVWGASVK, that targets ovarian cancer. This peptide accumulates in tumors, offering a promising new approach for targeted cancer therapy delivery.
Area of Science:
- Oncology
- Biotechnology
- Molecular Biology
Background:
- Targeted drug delivery enhances cancer therapy efficacy.
- Phage-displayed peptide libraries are valuable tools for identifying tumor-specific ligands.
- Ovarian cancer requires novel therapeutic strategies for improved patient outcomes.
Purpose of the Study:
- To isolate and characterize novel peptide ligands targeting human ovarian cancer.
- To evaluate the in vivo tumor-targeting capabilities of identified peptides.
- To assess the potential of peptide WSGPGVWGASVK for therapeutic agent delivery.
Main Methods:
- In vivo screening using phage-displayed peptide libraries.
- Intravenous injection of phage clone PC3-1 displaying peptide WSGPGVWGASVK in a tumor model.
- Immunohistochemical analysis to determine peptide distribution in tumor tissues and normal organs.
- In vitro binding and internalization assays using ovarian cancer cells and angiogenic endothelial cells.
- Flow cytometry to quantify peptide binding affinity (Kd value).
Main Results:
- A novel peptide, WSGPGVWGASVK (displayed by phage clone PC3-1), was identified.
- PC3-1 demonstrated significant accumulation in ovarian tumor sites with minimal uptake in normal organs.
- Immunostaining revealed PC3-1 binding to both tumor cells and tumor vasculature, indicating a diffuse tumor distribution.
- In vitro studies confirmed peptide WSGPGVWGASVK binds to and is internalized by tumor cells and angiogenic endothelial cells.
- Flow cytometry showed a dissociation constant (Kd) of 5.43 ± 0.4 μM for peptide binding to SKOV3 cells.
Conclusions:
- Peptide WSGPGVWGASVK exhibits specific targeting of ovarian tumors.
- The peptide effectively penetrates tumor sites and binds to tumor cells and vasculature.
- WSGPGVWGASVK is a promising lead candidate for developing targeted ovarian cancer therapeutics.
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