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Updated: Jul 10, 2026
Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
Targeting to tumor necrotic regions with biotinylated antibody and streptavidin modified liposomes
Abstract:
Tumor Necrosis Treatment (TNT) was developed to target solid tumors using monoclonal antibodies such as the chimeric TNT-3 monoclonal antibody (chTNT-3), which bind to degenerating cells located in necrotic regions of tumors. Since biotinylated chTNT-3 showed shorter circulating time and more uptakes in tumors than unmodified chTNT-3, we designed the two-step pretargeting approach composed of administering biotinylated chTNT-3 and 24 h later administering streptavidin modified liposomes encapsulating doxorubicin (DOX) to deliver DOX to the tumor site. The preservation of immunoreactivity of biotinylated chTNT-3 was confirmed by ELISA. The biological half-life of total DOX in two-step pretargeting approach was longer than that of free DOX but shorter than that of sterically stabilized liposomes in Sprague-Dawley rats. The two-step pretargeting approach regimen displayed good tumor targeting with a gradual process in biodistribution study. At 4 h and 24 h after administering DOX-loaded liposomes a highest DOX level of the two-step pretargeting approach was observed. The best antitumor efficacy was observed 3 days after the second treatment in Balb/c nude mice bearing H460 tumors. These results suggested the two-step pretargeting approach regimen may be a new form for delivering anticancer drugs to tumor necrotic regions.
Insights
This study introduces a two-step pretargeting approach using biotinylated antibodies and doxorubicin-loaded liposomes to effectively target solid tumors. This method shows promising anticancer efficacy by delivering drugs specifically to tumor necrotic regions.
Area of Science:
- Oncology
- Nanomedicine
- Immunotherapy
Background:
- Solid tumors present challenges for drug delivery due to necrotic regions.
- Monoclonal antibodies like chTNT-3 can target these necrotic tumor areas.
- Biotinylated antibodies offer improved tumor uptake compared to unmodified versions.
Purpose of the Study:
- To develop and evaluate a two-step pretargeting strategy for targeted delivery of doxorubicin (DOX) to solid tumors.
- To assess the efficacy and biodistribution of this novel drug delivery system.
Main Methods:
- Administering biotinylated chTNT-3 followed 24 hours later by streptavidin-modified liposomes encapsulating DOX.
- Confirming antibody immunoreactivity using ELISA.
- Evaluating DOX pharmacokinetics and biodistribution in Sprague-Dawley rats.
- Assessing antitumor efficacy in Balb/c nude mice bearing H460 tumors.
Main Results:
- The two-step pretargeting approach demonstrated effective tumor targeting.
- DOX exhibited a longer biological half-life compared to free DOX.
- Peak DOX levels were observed 4 and 24 hours after liposome administration.
- Significant antitumor efficacy was achieved 3 days post-treatment.
Conclusions:
- The two-step pretargeting approach is a viable strategy for targeted anticancer drug delivery to tumor necrotic regions.
- This method holds potential as a new therapeutic modality for solid tumors.
