Unlocking Novel Anticancer Strategies: Bioactive Hydrogels for Local Delivery of Plasma-derived Oxidants in an in ovo Cancer Model.

Cold Atmospheric Plasma (CAP) is a versatile tool in biomedicine due to its ability to generate reactive oxygen and nitrogen species (RONS). RONS can interact with biological targets, to induce beneficial therapeutic effects, e.g., disinfection, wound healing, and cancer treatment. In the field of plasma oncology, CAP-treated hydrogels (PTHs) are being explored for the local and precise administration of CAP-derived RONS as a novel anticancer approach. PTHs have shown anticancer effects in vitro, however, they have not yet been studied in more advanced and relevant cancer models. In this context, the present study explores for the first time the therapeutic potential of PTHs using an advanced in ovo cancer model. More specifically, PTHs composed of either alginate (Alg), gelatin (Gel), Alg/Gel combination, or Alg/hyaluronic acid (HA) combination were investigated. All chicken embryos survived the PTHs treatment, suggesting that the in ovo cancer model could become a time- and cost-effective tool for developing and optimizing anticancer therapeutic approaches involving hydrogels. On the macroscopic level (weight and vasculature), tumors showed no significant differences for different treatments/formulations. However, microscopic analysis of tumor sections revealed a notable reduction in CD44+ cell population and their proliferative state for the CAP-treated Alg-HA condition. Moreover, the CAP-treated Alg-HA formulation altered the extracellular matrix (ECM) composition, which may help combat drug-resistance. In conclusion, the present study validates the utility of in ovo cancer model for PTHs exploration and highlights the promising potential of injectable Alg-based PTHs containing HA and CAP-derived RONS for cancer treatment. This article is protected by copyright. All rights reserved.