BDB -BiopanningDataSet Details

Biopanning Data

BiopanningDataSet ID: 3512

Peptides:

Sequences	Affinity Values
CRQTKN(9/22) CRGTAEG(6/22) CKSRKDGAC(3/22) CMPKRPSSC(1/22)	[9.92179] [4.812447±0.023385] [3.667137±0.009220] [5.607913±0.032665]

Sequences Features:

Motif:

Unique Sequence Number:

Experimental Method:

Phage display (in vivo)

Sequencing Platform:

Sequencing Method:

Sanger sequencing

Rounds of Panning:

Reference:

PMID: 31243044

Target Name:

K-ras(LA2) mutant mouse model of lung cancer

Template Name:

Not determined.

Structure of Target-Template Complex:

Not determined.

Structure of Target-Peptide Complex:

Not determined.

Library Name:

T7 CX7C phage display library (CX7C)

Affinity Measurement Method:

Binding assay

Affinity Measurement Description:

Ex vivo fluorescence intensities were measured using the eXplore Optix and Analysis Workstation software (ART Inc.). Fluorescence intensities were reproduced from Figure 1C in the reference and shown. Data are presented as mean +/- SE.

Brief Description:

K-ras(LA2) mutant mice bearing lung tumors (18–20 weeks old) were intravenously injected with a solution containing phages at a total of 1e11 pfu. After 15 minutes of circulation, mice were sacrificed and tumor nodules from lungs were excised and weighed. Cell suspension of tumor nodules was prepared in culture media by chopping with a knife, homogenizing using Medimachine (DAKO), and passing through a 70 μm cell strainer. The cell bound phages were eluted by lysing cells with 100 mL of 1% NP-40 for 10 minutes on ice and then by adding BL21 host bacteria. Phages were amplified in the host bacteria and used for next round of selection.

BiopanningDataSet Comments:

Compared with other candidate peptides selected from 5 rounds of phage display, the CRQTKN peptide homed to tumor nodules in the lung of mutant mice at higher levels. Photoacoustic tomography of mutant mice detected lung tumors via tumor homing of the near-infrared fluorescence dye-labeled CRQTKN peptide. Ex vivo photoacoustic images of isolated organs further demonstrated tumor homing of the CRQTKN peptide, whereas minimal accumulation was observed in control organs, such as the liver. Compared with untargeted liposomes and doxorubicin, doxorubicin-loaded liposomes whose surface was modified with the CRQTKN peptide more efficiently delivered doxorubicin and reduced the number or size of tumor lesions in K-ras(LA2) mutant mice. Analysis of hematologic parameters and liver and kidney function showed no significant systemic side effects by the treatments. Affinity-based identification was used to detect TNF receptor superfamily member 19L (TNFRSF19L), which was upregulated in lung tumors of mutant mice, as the receptor for the CRQTKN peptide. In conclusion, these results suggest that the CRQTKN peptide is a promising targeting probe for photoacoustic-guided detection and drug delivery to lung cancer, and acts by binding to TNFRSF19L.

Curator:

Chunchao Pu

Curation Date:

2020-12-29

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