Fibrinogen-coated albumin nanospheres for mitigation of irradiation-induced wound healing impairment in breast cancer patients.

PROJECT SUMMARY Impaired wound healing after radiation therapy is a major clinical challenge in the management of oncologic patients. The efficacy of radiotherapy in cancer treatment is often accompanied by the disruption of biological pathways underlying the wound repair process, with considerable side effects represented by skin injuries and ulcers. At the same time, the need for complete wound healing after a surgical procedure could delay the administration of radiotherapy, essential for cancer remission, posing a potential threat to patients’ survival. Current clinical practice is limited to conservative management of irradiated wounds, without targeting the pathogenesis of impaired wound healing after radiation. Fibroplate has conceived Fibrinoplate-S (FPS), a solution based on intravenously injectable Fibrinogen-coated Albumin nano Spheres (FAS) with a unique multivalent potential to accelerate chronic wound healing in multiple soft tissues. Previous studies showed that FPS can accelerate the healing of Radiation Skin injuries by promoting mobilization of progenitor cells of various lineages including Endothelial Progenitor Cells (EPCs), and by regulating the levels of several cytokines involved in inflammatory states. By taking advantage of this knowledge, Fibroplate Inc. proposes to perform the first preclinical assessment of FPS efficacy to accelerate the healing of the surgical wound in oncologic patients undergoing radiotherapy. If confirmed, FPS could shorten the time window between surgery and RT by improving surgical wound healing with a positive impact on cancer treatment. In this SBIR Phase I project Fibroplate aims to achieve two objectives. 1) Demonstrate the ability of FPS to promote surgical wound healing after radiotherapy. A murine orthotopic metastatic breast cancer model will be used to mimic human breast cancer progression and treatment including mastectomy procedures. Wound closure and strength, cytokine panel, and degree of neovascularization will be assessed. The same model will also serve as validation of FPS’ mode of action. In particular, Fibroplate will validate the ability of FPS to induce mobilization of progenitor cells, which will confirm that the mode of action of FPS is not affected by the cancer environment. 2) Assess FPS’ safety profile on mice with a preliminary evaluation of its impact on coagulation parameters, and evaluation of health parameters including body weight and residual tumor mass (if any). This work will be preparatory of a Phase II project, where Fibroplate aims to perform additional IND-enabling studies to further characterize FPS’ dosing, efficacy, and safety profile in mice and minipigs cancer models.