Evaluation of the activity of a chemo-ablative, thermoresponsive hydrogel in a murine xenograft model of lung cancer

• Published in: British journal of cancer Vol. 123; no. 3; pp. 369 - 377
• Main Authors: Rossi, Seóna M., Ryan, Benedict K., Kelly, Helena M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.08.2020; Nature Publishing Group
• Subjects: 631/67/1612; 692/4028/67/1059/153; A549 Cells; Ablation Techniques; Animals; BALB 3T3 Cells; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Survival - drug effects; Cytotoxicity; Dose-Response Relationship, Drug; Drug Resistance; Epidemiology; Female; Humans; Hydrogels; Hydrogels - administration & dosage; Hydrogels - adverse effects; Hydrogels - pharmacokinetics; Kidneys; Lung cancer; Lung Neoplasms - blood; Lung Neoplasms - therapy; Mice; Molecular Medicine; Oncology; Poloxamer - administration & dosage; Poloxamer - adverse effects; Poloxamer - pharmacokinetics; Solid tumors; Thermodynamics; Treatment Outcome; Xenograft Model Antitumor Assays; Xenografts
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/s41416-020-0904-9

Background Minimally invasive intratumoural administration of thermoresponsive hydrogels, that transition from liquid to gel in response to temperature, has been proposed as a potential treatment modality for solid tumours. The aim of this study was to assess the inherent cytotoxicity of a poloxamer-based thermoresponsive hydrogel in a murine xenograft model of lung cancer. Methods In vitro viability assessment was carried out in a lung cancer (A549) and non-cancerous (Balb/c 3T3 clone A31) cell line. Following intratumoural administration of saline or the thermoresponsive hydrogel to an A549 xenograft model in female Athymic Nude-Foxn1nu mice ( n  = 6/group), localisation was confirmed using IVIS imaging. Tumour volume was assessed using callipers measurements over 14 days. Blood serum was analysed for liver and kidney damage and ex vivo tissue samples were histologically assessed. Results The thermoresponsive hydrogel demonstrated a dose-dependent cancer cell-specific toxicity in vitro and was retained in situ for at least 14 days in the xenograft model. Tumour volume increase was statistically significantly lower than saline treated control at day 14 ( n  = 6, p  = 0.0001), with no associated damage of hepatic or renal tissue observed. Conclusions Presented is a poloxamer-based thermoresponsive hydrogel, suitable for intratumoural administration and retention, which has demonstrated preliminary evidence of local tumour control, with minimal off-site toxicity.