Multimodal cancer diagnosis via living thrombocyte-nanodiamond hybrids

• Applicant: Dr.-Ing. Sascha Balakin
• Subject Area: Biomaterials
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 520543448

Cancer is one of the major challenges for global healthcare systems. Once detected, cancer surgery is still the gold standard for cancer treatment, where the surgical resection of tumours requires precise locating and defining of the margins between lesions and normal tissue. Particularly for cancer types with a high recurrence rate of 50-70 % after initial treatment, such as lung cancer. Novel treatments able to tackle this issue, such as fluorescence-guided surgery (FGS), rely on the efficiency of the contrast agents. Unfortunately, current contrast agents lack selectivity, photostability, and biocompatibility. The project CANDY aims to develop living hybrid materials using carbon-based contrast agents with stable photoluminescence (PL), activity in magnetic resonance imaging, cancer targeting, and immune evasion properties due to the living component. Therefore, fluorescent nanodiamonds (NDs) will be loaded into thrombocytes to shield the synthetic materials from immunosurveillance. Loaded thrombocytes will release the NDs upon their activation, where tumour cells mediate direct activation and adhesion of thrombocytes. The living component is responsible for shielding and delivery to the cancerous tissue, whereases the synthetic NDs will specifically label cancer cells to enable multimodal imaging. Prior to thrombocyte loading, NDs will be fused with an aptamer (MUC1) to target the surface receptor mucin 1, which is overexpressed on cancer cells. The systematic influence of mole ratio, time, pH, agglomerate size, and pre-treatment of NDs on their surface loading with MUC1 aptamers and PL will be determined. Within the present proposal, NDs, ND-MUC1, and ND-scrambled aptamer (non-specific binding control) conjugates will be loaded into the cytoplasm of thrombocytes via alpha granules to target lung cancer cells (A-549). Thrombocytes provide excellent circulation time in blood, biocompatibility, and in vivo selectivity compared to state-of-the-art carriers. In order to validate the living hybrid material and to translate the ND-thrombocyte system towards clinical applications, their hemocompatibility, in vitro uptake, and selectivity will be studied in a pre-clinical setup. The internalization of NDs will be performed under mild conditions, such as spontaneous cellular uptake or electroporation, to prevent the activation of the resting thrombocytes. The loaded thrombocytes will be stimulated, and the released ND conjugates will be transferred for in vitro assessment in A-549 and primary human bronchial epithelial (negative control) cells. With the focus on going beyond the current state of the art in cancer diagnosis and FGS, this project’s fundamental goal is to hybrid living materials for applications in oncology and beyond as a theragnostic platform.

• DFG Programme: Research Grants