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Updated: Jun 11, 2026
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Pre-clinical Orthotopic Murine Model of Human Prostate Cancer
Published on: August 29, 2016
Nanoparticle-induced vascular blockade in human prostate cancer
Lilach Agemy1, Kazuki N Sugahara, Venkata Ramana Kotamraju
1Vascular Mapping Laboratory, Center for Nanomedicine, Sanford-Burnham Medical Research Institute at the University of California at Santa Barbara (UCSB), Santa Barbara, CA, USA.
Blood
|July 1, 2010
Summary
Tumor-homing nanoparticles loaded with the CREKA peptide target and clot tumor blood vessels, inhibiting growth. This theranostic approach uses imaging to confirm tumor targeting and reduced blood flow, leading to necrosis and significant tumor reduction.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- The CREKA pentapeptide targets tumor vasculature by binding to fibrin.
- CREKA-coated nanoparticles induce self-amplifying clotting in tumor vessels, enhancing homing.
- Theranostic nanoparticles combine imaging and therapeutic capabilities for cancer treatment.
Purpose of the Study:
- To develop novel theranostic nanoparticles for simultaneous tumor imaging and growth inhibition.
- To enhance nanoparticle tumor homing and binding efficacy using modified peptides and nanoworm shapes.
- To investigate the self-amplifying clotting effect for targeted tumor vascular obstruction.
Main Methods:
- Conjugation of the CREKA peptide and CRKDKC peptide to superparamagnetic iron oxide nanoparticles.
- Fabrication of elongated nanoparticles (nanoworms) for improved binding.
- Modification of the CREKA peptide with nonproteinogenic residues to increase circulation stability.
- In vivo studies in mice with orthotopic human prostate cancer xenografts.
- Multimodal imaging (optical, MRI, ultrasound) for tumor targeting and vascular assessment.
- Evaluation of tumor growth, necrosis, and blood flow reduction post-treatment.
Main Results:
- Targeted nanoworms induced extensive clotting specifically in tumor vessels, not in normal tissues.
- Multimodal imaging confirmed precise tumor targeting and significant reduction in tumor blood flow.
- Modified CREKA peptide enhanced nanoparticle stability and circulation efficacy.
- Multiple doses of nanoworms led to significant tumor growth inhibition and induced tumor necrosis.
Conclusions:
- The developed CREKA-CRKDKC nanoworms represent a promising theranostic platform for cancer treatment.
- The self-amplifying clotting mechanism effectively obstructs tumor vasculature, inhibiting growth.
- This approach offers a dual modality of imaging and therapy with high tumor specificity.
