In vitro Determination of the Therapy and Detection Potential of Zr-89 Labeled Docetaxel Loaded Nanoplatform on Triple-Negative Breast Cancer Cells

Project no. 22274 · Status: Kapanmış · 2020

Summary

Breast cancer is one of the most common diseases worldwide, predominantly affecting women, and it is the second leading cause of cancer-related death. Triple-negative breast cancer (TNBC) has limited treatment due to the lack of HER-2/neu, progesterone, and estrogen receptors. TNBC is also more aggressive than other cancer forms. The chemotherapy method, which is used to recover the patient’s life, is insufficient for TNBC routine treatment. For this reason, it is promising that monoclonal antibodies (mAb) and drug delivery nanosystems are targeted to tumor-specific targeting. There are different combinations currently used in the clinic. Considering the success of FDA-approved nab-Paclitaxel (Abraxane), the current application of Docetaxel (DTX) in the neo-adjuvant and adjuvant treatment of TNBC and the fact that it is not yet in a combination like nab-Paclitaxel, the design of this nanoplatform designed in the project is aimed. There are numerous clinical uses of each component—HSA, Docetaxel, and DVL in the nanoplatform. However, no research has been done on DTX-loaded HSA nanoplatforms that are targeted by DVL. For this reason, in our project, human serum albumin (HSA) nanoparticle was chosen as the delivery of the anti-cancer drug Docetaxel (DTX). An effective nanoplatform (HSA-DTX@PEG-DVL) was synthesized in targeted TNBC cells with Durvalumab (DVL), which is effective in the PD-L1 pathway. It is revealed that the nanoplatform has target-directed chemotherapeutic activity with in vitro experiments. Additionally, the prepared HSA-DTX@PEG-DVL nanoplatform was labeled with 89Zr, and its potential as an immunoPET agent was evaluated by in vitro experiments (89Zr-DVL-PEG@HSA-DTX). The development of nanostructures radiolabeled with 89Zr for use in nuclear medicine enhances the nanoplatform's application possibilities.  Therefore, it is expected that the capability of becoming a targeted chemotherapeutic and immune-PET agent for the treatment of TNBC in a single HSA-DTX@PEG-DVL nanoplatform will serve as the foundation for the design of a novel multifunctional agent and the basis for ongoing preclinical investigations.

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