Treating colorectal peritoneal metastases with an injectable cytostatic loaded supramolecular hydrogel in a rodent animal model.

Autor: Wintjens AGWE; Department of Surgery, Maastricht University Medical Centre, PO Box 5800, Maastricht, 6202 AZ, The Netherlands.; NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands., Liu H; Department of Surgery, Maastricht University Medical Centre, PO Box 5800, Maastricht, 6202 AZ, The Netherlands.; NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands., Fransen PKH; UPyTher BV, Eindhoven, The Netherlands., Lenaerts K; Department of Surgery, Maastricht University Medical Centre, PO Box 5800, Maastricht, 6202 AZ, The Netherlands.; NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands., van Almen GC; UPyTher BV, Eindhoven, The Netherlands., Gijbels MJ; NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.; Department of Pathology, Maastricht University Medical Centre, Maastricht, The Netherlands.; Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Infection and Immunity, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center, Amsterdam, The Netherlands., Hadfoune M; NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands., Boonen BTC; NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands., Lieuwes NG; Department of Precision Medicine, Maastricht University, Maastricht, The Netherlands., Biemans R; Department of Precision Medicine, Maastricht University, Maastricht, The Netherlands., Dubois LJ; Department of Precision Medicine, Maastricht University, Maastricht, The Netherlands., Dankers PYW; Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands.; Department of Biomedical Engineering, Laboratory of Chemical Biology, Eindhoven University of Technology, Eindhoven, The Netherlands., de Hingh IHJT; GROW - School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands.; Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands., Bouvy ND; Department of Surgery, Maastricht University Medical Centre, PO Box 5800, Maastricht, 6202 AZ, The Netherlands. n.bouvy@mumc.nl.; GROW - School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands. n.bouvy@mumc.nl.
Jazyk: angličtina
Zdroj: Clinical & experimental metastasis [Clin Exp Metastasis] 2023 Jun; Vol. 40 (3), pp. 243-253. Date of Electronic Publication: 2023 May 22.
DOI: 10.1007/s10585-023-10210-0
Abstrakt: Patients with peritoneal metastases (PM) of colorectal cancer have a very poor outcome. Intraperitoneal delivery of chemotherapy is the preferred route for PM treatment. The main limitation of the treatment options is the short residence time of the cytostatic, with subsequent short exposure of the cancer cells. To address this, a supramolecular hydrogel has been developed that allows both local and slow release of its encapsulated drug, mitomycin C (MMC) or cholesterol-conjugated MMC (cMMC), respectively. This experimental study investigates if drug delivery using this hydrogel improves the therapeutic efficacy against PM. PM was induced in WAG/Rij rats (n = 72) by intraperitoneally injecting syngeneic colon carcinoma cells (CC531) expressing luciferase. After seven days, animals received a single intraperitoneal injection with saline (n = 8), unloaded hydrogel (n = 12), free MMC (n = 13), free cMMC (n = 13), MMC-loaded hydrogel (n = 13), or cMMC-loaded hydrogel (n = 13). Primary outcome was overall survival with a maximum follow-up of 120 days. Intraperitoneal tumor development was non-invasive monitored via bioluminescence imaging. Sixty-one rats successfully underwent all study procedures and were included to assess therapeutic efficacy. After 120 days, the overall survival in the MMC-loaded hydrogel and free MMC group was 78% and 38%, respectively. A trend toward significance was found when comparing the survival curves of the MMC-loaded hydrogel and free MMC (p = 0.087). No survival benefit was found for the cMMC-loaded hydrogel compared to free cMMC. Treating PM with our MMC-loaded hydrogel, exhibiting prolonged MMC exposure, seems effective in improving survival compared to treatment with free MMC.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz: