Related Experiment Video
Updated: Jun 22, 2026
Generation of an Orthotopic Xenograft of Pancreatic Cancer Cells by Ultrasound-Guided Injection
Published on: November 1, 2021
Using in vivo biopanning for the development of radiation-guided drug delivery systems
Jerry J Jaboin1, Zhaozhong Han, Dennis E Hallahan
1Department of Radiation Oncology, Vanderbilt University, Nashville, TN, USA.
Abstract:
This chapter illustrates our protocol for in vivo biopanning using T7 bacteriophage libraries for the purpose of selecting recombinant peptides for the tumor-specific delivery of radiosensitizers to radiation-inducible antigens within tumor neovasculature. Our goal is to discover peptides binding within tumor vascular endothelium of irradiated tumors. We have previously demonstrated that tumor irradiation increases the spectrum of antigenic targets for drug delivery. To identify candidate peptides with the ability to bind radiation-induced antigens, we inject the phage peptide library intravenously into mice bearing irradiated GL261 and Lewis lung carcinoma (LLC) hind limb tumors. Phage are recovered from excised tumors, amplified, and readministered to mouse-bearing tumors for six total rounds. At least 50 bacterial colonies are selected from each of the tumor types, and prioritized. This prioritization is based on their relative concentrations in tumor versus normal tissues, and then assessment of dominant phage present in both tumor types. These phage are amplified, and the gene sequences determined to deduce the recombinant peptide product. Further prioritization is performed by fluorescence labeling of the selected phage, and injection into irradiated and mock-irradiated tumor-bearing mice for evaluation of in vivo targeting of the candidate phage/peptides.
Insights
This study details a method for selecting tumor-targeting peptides using T7 bacteriophage libraries. These peptides aim to deliver radiosensitizers to radiation-induced antigens in tumor neovasculature for enhanced cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Tumor irradiation enhances antigenic targets for drug delivery.
- Radiosensitizers improve radiation therapy efficacy.
- Targeted delivery of radiosensitizers can minimize systemic toxicity.
Purpose of the Study:
- To develop a protocol for in vivo biopanning using T7 bacteriophage libraries.
- To select recombinant peptides that bind to radiation-inducible antigens in tumor neovasculature.
- To identify peptides for tumor-specific delivery of radiosensitizers.
Main Methods:
- Intravenous injection of T7 phage peptide library into mice with irradiated GL261 and Lewis lung carcinoma tumors.
- Phage recovery from excised tumors, amplification, and repeated administration for six rounds.
- Prioritization of phage based on tumor vs. normal tissue concentration and dominant phage presence, followed by gene sequencing.
Main Results:
- Selection of candidate phage/peptides with potential for binding radiation-induced antigens.
- Identification of phage enriched in tumor tissues compared to normal tissues.
- In vivo evaluation of candidate phage/peptide targeting in irradiated and mock-irradiated tumor-bearing mice.
Conclusions:
- The described in vivo biopanning protocol is effective for selecting peptides targeting tumor neovasculature.
- Selected peptides show potential for targeted delivery of radiosensitizers to irradiated tumors.
- This approach facilitates the discovery of novel agents for improving cancer radiotherapy.
More Related Videos
Related Concept Videos
01:09Methods for Studying Drug Absorption: In situ
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
01:24Modified-Release Drug Delivery Systems: Site-Targeted