Phenotype independent capture of circulating tumor cell using magnetic platelet decoys

Abstract

Circulating tumor cells (CTCs) are an essential biomarker for metastatic disease as they provide valuable information regarding the primary tumor, metastatic potential, potential prognosis, as well as aid in patient monitoring and guiding personalized therapy. Successful detection, isolation, and enumeration of CTCs remains a challenge due to their rarity in blood and biological heterogeneity. Though traditionally known for their roles in maintaining hemostasis and promoting wound healing, platelets significantly contribute to cancer metastasis by interacting with CTCs in the bloodstream. These interactions protect CTCs from shear stress and immune detection, facilitate their arrest in blood vessels, and ultimately promote metastatic spread to distant tissues. We describe a system that leverages platelet-cancer cell interactions to target and retrieve CTCs from a liquid biopsy sample by engineering magnetic platelet decoys. Conventional techniques typically rely on specific markers on the CTC surface (most commonly EpCAM). Our approach begins with engineering platelet decoys that lose their functional ability but retain some functional surface receptors that enable their ability to interact with other cells, followed by ION (iron oxide nanoparticle) loading which permits CTC capture via magnetic retrieval. Because our non-antibody-based approach relies on magnetic platelet decoy-CTC interactions, we infer that our system is applicable to CTCs of various origins and phenotypes. We have characterized and shown that our system can effectively interact with various cell lines (MDA-MB-231, MCF-7, A549) and capture these cells in spiked whole blood with a retrieval rate of at least 58.5%. This study has also demonstrated that the magnetic platelet decoys remain stable and effective after cryopreservation. While experiments used freshly prepared magnetic platelet decoys, stability assessment demonstrated that magnetic platelet decoys stored for one month at −20 °C with cryoprotectant retain their activity and ability to interact with other cells, supporting their practical use in future applications.